6.1. Introduction

ART has reduced mortality and morbidity associated with HIV and transformed HIV into a chronic disease requiring lifetime care. Coinfections and comorbidities, including physical and mental health conditions and substance use disorders, are common among people living with HIV. Comprehensive HIV care includes combination HIV prevention, the promotion of general health and well-being, maintaining quality of life and screening, ART, and the prevention and management of coinfections and comorbidities.

This chapter provides a brief overview of common and important concomitant conditions among people living with HIV. This includes information on co-trimoxazole prophylaxis, the diagnosis, prevention and treatment of TB, viral hepatitis, malaria, sexually transmitted infections, cervical cancer prevention, nutrition, vaccinations, mental health and substance use. It summarizes selected key recommendations, good practice statements and related materials from existing WHO guidelines. Sources are provided for relevant previously published recommendations where more detailed information on their management can be found.

6.2. General care for people living with HIV

One in four adults and four of five adolescents do not get enough physical activity and 4–5 million deaths per year could be averted if global populations were more physically active (2). WHO has produced evidence-informed guidelines and recommendations on the health effects of physical activity and sedentary behaviour that governments can adopt as part of their national policy frameworks (1). The guidelines provide a cost-effective option that regions, countries or subnational authorities can adapt and use. For adults, physical activity confers benefits for the following health outcomes: reduced all-cause mortality, cardiovascular disease mortality, incident hypertension, incident site-specific cancer,¹ incident type 2 diabetes, improved mental health (reduced symptoms of anxiety and depression), cognitive health and sleep; measures of adiposity may also improve (1).

Countries should establish a package of general HIV care interventions, in addition to ART, for people living with HIV to reduce HIV transmission, prevent illness and improve their quality of life. General care includes combination HIV prevention, promoting the health of people living with HIV and screening for, prophylaxis for and management of coinfections and comorbidities. WHO has produced summary guidance on general care and prevention interventions (3–5) and recommends a package of 13 prevention interventions for adults and adolescents living with HIV in resource-limited settings:

• psychosocial counselling and support;
• disclosure and partner notification;
• co-trimoxazole prophylaxis;
• TB counselling, screening and preventive therapy;
• preventing common fungal infections;
• preventing sexually transmitted infections and supporting reproductive health needs, including preventing and screening for cervical cancer;
• malaria: co-trimoxazole, bed nets and preventing malaria among pregnant women;
• selected vaccine-preventable diseases;
• nutrition;
• family planning;
• prevention of mother-to-child HIV transmission;
• needle and syringe programmes for people who inject drugs; and
• water sanitation and hygiene.

A general care package will vary according to the type of epidemic, populations affected and prevalence of coinfections, other comorbidities and health conditions. Table 6.1 provides an overview of elements of a general care package for people living with HIV. In the era of universal treatment for all people living with HIV, the time between HIV diagnosis, enrolment into care and initiation of ART may be limited to a single visit to reduce loss to follow-up and to provide life-saving ART as soon as possible. WHO no longer recommends the need for preparatory visits before initiating ART; many of the care aspects outlined in Table 6.1 can be accomplished once ART has started (4,5).

Table 6.1

Overview of key elements of general care over the continuum of HIV care for people living with HIV.

6.3. Co-trimoxazole prophylaxis

Background and rationale

Co-trimoxazole is a fixed-dose combination of two antimicrobial agents (sulfamethoxazole and trimethoprim) used to treat a variety of bacterial, fungal and protozoan infections. Co-trimoxazole prophylaxis is a feasible, well-tolerated and inexpensive intervention to reduce HIV-related morbidity and mortality among people living with HIV. Co-trimoxazole is an off-patent drug and is widely available in resource-limited settings.

In 2006, the first WHO guidelines on co-trimoxazole prophylaxis in resource-limited settings recommended co-trimoxazole prophylaxis as an integral component of HIV care (7). These guidelines were reviewed in 2014 and updated in the context of expanded access to and earlier initiation of ART (6). In recent years, new evidence has emerged showing that, with expanded access to ART, co-trimoxazole prophylaxis has broader benefits beyond preventing some AIDS-associated opportunistic diseases (Pneumocystis jirovecii pneumonia and toxoplasmosis) and reducing HIV-associated mortality among people with low CD4 cell counts. These benefits relate to preventing malaria and severe bacterial infections among adults and children living with HIV.

Nine observational studies (8–16) provide moderate-certainty evidence to support the effectiveness of co-trimoxazole prophylaxis in reducing death among people starting ART with CD4 cell count at or below 350 cells/mm³ and/or WHO clinical stage 3 or 4 disease. In addition, a new expanded recommendation for using co-trimoxazole prophylaxis is based on a systematic review showing the effectiveness of co-trimoxazole prophylaxis in reducing mortality, severe bacterial infections, malaria and hospitalization among adults and adolescents with HIV regardless of clinical and immunological parameters (17). One randomized clinical trial involving children living with HIV showed survival benefits regardless of age and CD4 cell count and also supports the expansion of co-trimoxazole prophylaxis to children, especially in settings with high prevalence of malaria and/or severe bacterial infections (18,19).

Continuing co-trimoxazole prophylaxis regardless of ART status, age, CD4 cell count or WHO clinical stage in settings with high prevalence of malaria and/or severe bacterial infections is also recommended based on data from randomized controlled trials that show a significant reduction in the risk of hospitalization, malaria and diarrhoea among adults and children with HIV in settings with high prevalence of malaria and/or severe bacterial infections (20,21). In addition, the recommendation to continue co-trimoxazole prophylaxis in settings with a high prevalence of malaria and/or severe bacterial infections may simplify HIV management, forecasting and supply management issues and improve access to co-trimoxazole prophylaxis access for people living with HIV.

The risks and benefits of continuing versus stopping co-trimoxazole prophylaxis after viral suppression induced by ART were also evaluated in settings with a low burden of malaria and severe bacterial infections. Two studies found that the rates of Pneumocystis jirovecii pneumonia and death were similar for people receiving ART who achieved suppressed viral loads and had CD4 cell counts above 100 cells/mm³ in study arms (22,23). In these settings, discontinuing co-trimoxazole prophylaxis for adults based on clinical, immunological and virological parameters indicating ART immune recovery can be considered, although the certainty of the evidence is low to very low (6). However, in settings with a low prevalence of malaria and/or severe bacterial infections and limited or no access to CD4 cell testing, co-trimoxazole prophylaxis should not be discontinued.

The recommendation on women and adolescents living with HIV using co-trimoxazole prophylaxis during pregnancy to prevent malaria complications and avoid simultaneous intermittent preventive treatment is based on a systematic review showing that co-trimoxazole prophylaxis is not inferior to intermittent preventive treatment of malaria in pregnancy with respect to mortality, low birth weight, placental malaria, maternal deaths and severe adverse events (24). The recommendation to discontinue co-trimoxazole prophylaxis at the end of the risk period for transmission in infants who are HIV-exposed and uninfected is also maintained, but new evidence has emerged on the lack of clinical benefits of co-trimoxazole prophylaxis for HIV-exposed infants who are uninfected and on the potential harm associated with disrupting the microbiome and selecting antibiotic resistance. Where HIV vertical transmission is very uncommon and HIV infection can be reliably excluded, consideration has been given to shorten administration of co-trimoxazole in infants who are HIV exposed but uninfected (see Box 6.1). WHO anticipates reviewing this recommendation as further evidence is gathered and increasing progress is made to rapidly identify infants living with HIV and to retain those exposed to HIV in the testing cascade until final diagnosis is ascertained.

Box 6.1Using co-trimoxazole among infants who are HIV exposed but uninfected

Since WHO revised the co-trimoxazole guidelines in 2013, new evidence has emerged on the lack of clinical benefits of co-trimoxazole prophylaxis for HIV-exposed infants. A systematic review (25) was undertaken to assess the effect of co-trimoxazole prophylaxis on morbidity and mortality among HIV-exposed and uninfected infants. Only two trials from Botswana and South Africa were identified (26,27).

The randomized trial in Botswana (co-trimoxazole n = 1423; placebo n = 1425) gave co-trimoxazole from 14–34 days until 15 months and showed no evidence of benefit of co-trimoxazole for HIV-exposed and uninfected children for cumulative mortality to 18 months (30 deaths [2.4%] for co-trimoxazole versus 34 deaths [2.6%] for placebo; difference −0.2%, 95% CI −1.5% to 1.0%; primary outcome) or hospitalization, diarrhoea or pneumonia (secondary outcomes; P > 0.05). The randomized trial in South Africa (co-trimoxazole n = 611; no co-trimoxazole n = 609), designed as a non-inferiority trial, gave co-trimoxazole from six weeks until infants were confirmed HIV-uninfected at the end of the at-risk HIV period and showed non-inferiority of not giving co-trimoxazole to HIV-exposed and uninfected children on combined grade 3 and 4 pneumonia, diarrhoea and all-cause mortality by 12 months (primary outcome 49 [8%] events [co-trimoxazole] versus 39 [6%] events [no co-trimoxazole]; risk difference no co-trimoxazole minus co-trimoxazole −0.032, 95% CI −0.075 to 0.011) or pneumonia, diarrhoea and mortality separately (P > 0.05). The groups did not differ in anaemia, but one study found that neutropaenia was more frequent in the co-trimoxazole group (26).

Substudies within these trials investigated bacterial resistance and found that the proportion of co-trimoxazole-resistant gastrointestinal bacteria was higher in the co-trimoxazole group (28), and co-trimoxazole prophylaxis decreased gut microbiome β-diversity and increased antibiotic resistance gene α-diversity and prevalence (29). Three further studies examined using co-trimoxazole prophylaxis to prevent malaria (30–32), all in Uganda. These studies found that co-trimoxazole prophylaxis protected against malaria among HIV-exposed and uninfected children when continued after breastfeeding ended, but mortality, hospitalization, diarrhoea and pneumonia were unaffected.

To critically review the evidence and explore potential implications for country programmes, WHO convened a technical expert group in March 2021. The group examined current estimates and trends for preventing HIV vertical transmission and coverage of infant testing, noting persisting gaps in timely identification and retention of infants in the testing-to-treatment cascade, with vertical transmission increasingly occurring postnatally. Current co-trimoxazole prophylaxis guidelines provide protection for children at high risk of acquiring HIV who may be missed by infant testing services, but as the systematic review findings suggest, if HIV infection can be reliably excluded, co-trimoxazole does not provide additional benefit to HIV-exposed but uninfected infants and children and may disrupt their microbiomes and increase antibiotic resistance to co-trimoxazole and other widely used antibiotics. This led the South African Thoracic Society to change their guidelines to no longer recommend co-trimoxazole prophylaxis for HIV-exposed and uninfected children (33). However, the studies included in the systematic review were undertaken in Botswana and South Africa, and these findings have limited generalizability to epidemic settings with higher vertical HIV transmission rates, poorer infant testing coverage, higher burden of malaria and other severe bacterial infections and higher infant mortality.

To further explore the potential impact of different approaches across epidemic settings, the group examined the output of a modelling study designed to help quantify the predicted impact of alternative co-trimoxazole strategies on death among HIV-exposed and uninfected children at age two years (34). Assuming full co-trimoxazole uptake, changing current guidelines was predicted to increase mortality in all settings. However, the benefits of the current policy are expected to be greatest in settings with substantial vertical transmission and poor infant testing coverage, in contrast to settings with low vertical transmission and very good infant testing, in which a strategy of shorter co-trimoxazole administration may be a reasonable alternative. This model did not include potential harm associated with disrupting the microbiome and selecting for antibiotic resistance because of the lack of clear clinical correlates.

Current WHO guidelines recommend starting co-trimoxazole for all HIV-exposed infants at age 4–6 weeks and stopping after the period of risk and final confirmation of a negative HIV status, defined as a negative 18-month test or testing after breastfeeding ends if breastfed longer than 18 months. Overall, the expert group thought that the evidence reviewed is compelling, but programme implementation remains challenging in many settings. The group considered fully revising the current recommendations to be premature but the group acknowledged that co-trimoxazole prophylaxis may be discontinued at the end of the at-risk period for HIV transmission (after breastfeeding ends and once HIV infection is ruled out by age-appropriate HIV testing), which may occur before 18 months.

Further, in settings with low vertical transmission rates, high HIV infant diagnosis coverage and strong retention in the testing-to-treatment cascade, country programmes may consider stopping providing routine co-trimoxazole as soon as HIV infection is ruled out by age-appropriate HIV testing (see Chapter 2).

Several gaps remain on how to optimize the use of co-trimoxazole prophylaxis among HIV-exposed infants to provide the highest impact. These gaps include optimal timing to start co-trimoxazole; clinical and programmatic impact of shorter duration of co-trimoxazole prophylaxis in different epidemic contexts and programmatic realities; the added value of potential differentiated approaches to co-trimoxazole prophylaxis delivery; the potential impact of shorter co-trimoxazole strategies on retention in the testing-to-treatment cascade; alternative antibiotic prophylactic regimens (other antibiotics); the clinical relevance of the selection of antibiotic resistance associated with co-trimoxazole prophylaxis; and the short- and long-term clinical relevance of the microbiome disruption resulting from co-trimoxazole prophylaxis. Although a randomized blinded clinical trial may not be required to address some of these questions, well-conducted operational research will be critical to innovate and better inform children’s use of co-trimoxazole prophylaxis in the future.

Table 6.2 summarizes the criteria for initiating and discontinuing co-trimoxazole prophylaxis for adults, adolescents, pregnant women and children living with HIV.

Table 6.2

Criteria for initiating and discontinuing co-trimoxazole prophylaxis.

6.4. Tuberculosis

6.4.1. Screening and diagnosis

Systematic screening for TB among people living with HIV

Recommendation (2021)

People living with HIV should be systematically screened for TB disease at each visit to a health facility (strong recommendation, very-low-certainty evidence).

Source: WHO consolidated guidelines on tuberculosis. Module 2: Screening: systematic screening for tuberculosis disease (41).

Tools for screening for TB among people living with HIV

Recommendations (2021)

Among adults and adolescents living with HIV, systematic screening for TB disease should be conducted using the WHO-recommended four-symptom screen, and those who report any one of the symptoms of current cough, fever, weight loss or night sweats may have TB and should be evaluated for TB and other diseases (strong recommendation, moderate-certainty evidence).

Among children younger than 10 years who are living with HIV, systematic screening for TB disease should be conducted using a symptom screen including any one of the symptoms of current cough, fever, poor weight gain or close contact with a person with TB disease (strong recommendations, low-certainty evidence for test accuracy).

Among adults and adolescents living with HIV, C-reactive protein with a cut-off of >5 mg/L may be used to screen for TB disease (conditional recommendation, low-certainty evidence for test accuracy).

Among adults and adolescents living with HIV, chest X-ray may be used to screen for TB disease (conditional recommendation, moderate-certainty evidence for test accuracy).

Among individuals aged 15 years and older in populations in which TB screening is recommended, computer-aided detection software programmes may be used in place of human readers for interpreting digital chest X-rays for screening and triage for TB disease (conditional recommendation, low-certainty evidence).

Among adults and adolescents living with HIV, molecular WHO-recommended rapid diagnostic tests may be used to screen for TB disease (conditional recommendation, moderate-certainty evidence for test accuracy).

Adult and adolescent inpatients with HIV in medical wards where the TB prevalence is >10% should be tested systematically for TB disease with a molecular WHO-recommended rapid diagnostic test (strong recommendation, moderate-certainty evidence for test accuracy).

Source: WHO consolidated guidelines on tuberculosis. Module 2: Screening: systematic screening for tuberculosis disease (41).

Summary of evidence and rationale

In 2019, an estimated 44% of people living with HIV who also had TB disease did not reach care, and TB caused 30% of all HIV-related deaths (2). Thus, ensuring early detection and treatment for TB among all people living with HIV is crucial for reducing morbidity and mortality.

The recommendation to systematically screen for TB disease at each visit to a health facility, which applies to people of all ages, along with the recommendations on related symptom screening algorithms for adults and adolescents and for children, was first published in 2011 in WHO’s Guidelines for intensified tuberculosis case-finding and isoniazid preventive therapy for people living with HIV in resource-constrained settings (19,44). For adults and adolescents, the WHO-recommended four-symptom screen is recommended. If an individual screens positive on any of the following four symptoms: current cough, fever, night sweats and weight loss, they should receive further diagnostic work-up. For children, any of the following symptoms would indicate diagnostic work-up for TB: current cough, fever, poor weight gain or close contact with a person with TB disease.

An individual participant data meta-analysis was conducted in 2020 to review the accuracy of the WHO-recommended four-symptom screen and other tools for TB screening among adults and adolescents, including C-reactive protein, chest X-ray and molecular WHO-recommended rapid diagnostic tests.

WHO four-symptom screen

The meta-analysis of individual patient data found no alternative screening tools or strategies that were significantly higher in both sensitivity and specificity than the WHO-recommended four-symptom screen. In all cases, when sensitivity was higher and met the minimal requirements of the target product profile for a screening test, the specificity was compromised and vice versa. Although the WHO-recommended four-symptom screen may have real-life limitations in terms of consistency and quality of delivery that might not be reflected in studies, it remains the simplest non-invasive tool to implement in any setting, requiring no infrastructure. However, the high proportion of positivity (94%) and very low specificity among medical inpatients living with HIV in settings where the TB prevalence among study participants was >10% gives it limited utility as a screen to rule in TB before diagnostic confirmation by molecular WHO-recommended rapid diagnostic tests in this very ill population. The review also found that the WHO-recommended four-symptom screen had reduced specificity for people not receiving ART (37%, 95% CI 25–59%) and reduced sensitivity for outpatients receiving ART (53%, 95% CI 36–69%). Programmes might therefore want to supplement the WHO-recommended four-symptom screen with other screening tools.

C-reactive protein

The analysis found that C-reactive protein was most accurate among outpatients living with HIV not receiving ART. When performed after a positive WHO-recommended four-symptom screen, C-reactive protein with a cut-off of >5 mg/L was found to be as sensitive as the WHO-recommended four-symptom screen, with a sensitivity of 78% (95% CI 70–85%) but with significantly higher specificity (73%; 95% CI 66–79%) than the WHO-recommended foursymptom screen, which had a sensitivity of 84% (95% CI 75–90%) and specificity of 37% (95% CI 25–50%).

Chest X-ray

The parallel combination of the WHO-recommended four-symptom screen and chest X-ray, in which a positive result from either tool should be followed up by diagnostic confirmation, had the highest sensitivity (85%, 95% CI 69–94%) compared with other tools including the WHO-recommended four-symptom screen (53%, 95% CI 36–69%) when used to screen for TB among outpatients receiving ART.

Computer-aided detection of chest X-ray

Studies comparing the accuracy of computer-aided detection software showed considerable variability among readers, but the substantial overlap of confidence intervals between computer-aided detection software and human readers suggested little difference in accuracy. Limited data were available for comparing computer-aided detection to human interpretation of chest X-ray among people living with HIV; further evidence is needed about the performance of computer-aided detection software among people living with HIV, to enable better setting-specific and patient-specific calibration of computer-aided detection software.

Diagnosing TB

The clinical picture of TB disease is often non-specific and in isolation does not enable its accurate diagnosis, requiring bacteriological testing for all people with signs and symptoms of TB disease. People living with HIV may have an atypical clinical picture, especially those with advanced disease, further complicating the clinical diagnosis of pulmonary and extrapulmonary forms of TB disease.

The diagnostic options recommended by WHO (42) are of two broad groups, either initial test for diagnosing TB, often with at least rifampicin resistance detection or those used for follow-on testing after TB confirmation. The latter aimed at detecting additional drug resistance once a TB diagnosis is made and is not covered in this section but covered in the relevant TB guidelines.

Rapid and accurate diagnosis is essential to ensure that people with TB are effectively treated and cured. Table 6.3 shows the initial tests WHO currently recommends. All have recommendations for use among people living with HIV and are considered as WHO rapid diagnostic tests. Furthermore, all are molecular WHO-recommended rapid diagnostic tests except for the lateral flow lipoarabinomannan (LF-LAM) test. Molecular WHO-recommended rapid diagnostic tests are recommended as an initial test rather than smear microscopy or culture, and the diagnostic algorithm 1 provided in the appropriate operational handbook should be followed (42).

LF-LAM is an add-on test specifically for people living with HIV, and the recommendations vary by the presence or absence of symptoms, CD4 cell count and severity of disease requiring hospitalization or not. It is a point-of-care test performed on a urine sample and suited for use as part of the standard package of care for advanced HIV disease. The respective TB guidelines and the accompanying handbook (42) provide details. In the latter, algorithms 2a and 2b provide the patient pathways for using LF-LAM for inpatients and outpatients. A positive LF-LAM test predicts mortality, and using the test in advanced HIV accompanied by appropriate and effective treatment saves lives. Next-generation tests with improved sensitivity, including patients with CD4 counts greater than 200 cells/mm³, have not yet reached commercialization. However, once available and reviewed, these tests offer the potential for broader use within people living with HIV.

Molecular WHO-recommended rapid diagnostic tests are the essential starting-point for diagnosing TB. They include nine different products, with most including simultaneous detection of at least rifampicin resistance. The Xpert® MTB/RIF and Xpert® MTB/RIF Ultra (Xpert® Ultra) have specific recommendations for people living with HIV and extrapulmonary TB. The Xpert® Ultra is more sensitive than the Xpert® MTB/RIF, including for people living with HIV, accompanied by slightly lower specificity. The lower specificity is associated with a previous history of TB treatment in the past five years, mainly when a very low bacterial load is detected, and this semiquantitative result is called “trace”. TB DNA may trigger this test result from non-viable organisms among people previously treated, thus being false positive for TB disease.

The Truenat™ and Truenat™ plus tests are suited to similar care levels to the Xpert® and Ultra. Testing for rifampicin is performed as a follow-on reflex test on the same instruments. The TB-LAMP does not test for rifampicin resistance and is thus best suited for areas with a low prevalence of multidrug- and rifampicin-resistant TB. In addition, it requires more hands-on time than other molecular WHO-recommended rapid diagnostic tests. However, it is less expensive both in test costs and equipment than other molecular WHO-recommended rapid diagnostic tests.

The latest addition to the recommended group of molecular WHO-recommended rapid diagnostic tests as initial diagnostic test is the class of moderate complexity automated nucleic acid amplification tests (NAATs). These tests have comparable sensitivity and specificity with other molecular WHO-recommended rapid diagnostic tests in detecting TB and detect resistance to rifampicin and isoniazid. However, this class of tests requires laboratory infrastructure with a rapid and reliable specimen transport system. The class include systems that can perform between 24 and 96 samples in a single run, making it suitable for use in higher-throughput and urban settings. Importantly, this class now includes four new products, all of which have SARS-CoV-2 testing available. Two are widely used for HIV testing and thus facilitate the use of common platforms where capacity exists. The list of products is Abbott RealTime RealTime MTB and MTB RIF/INH assays (Abbott Laboratories, Abbott Park, IL, USA), the BD MAX™ multidrug-resistant TB assay (Becton, Dickinson and Company, Franklin Lakes, NJ, USA), the Hain FluoroType® MTBDR assay (Bruker/Hain Lifescience, Nehren, Germany) and the Roche COBAS® MTB and MTB-RIF/INH assays (F. Hoffmann-La Roche, Basel, Switzerland).

All the molecular WHO-recommended rapid diagnostic tests are recommended for diagnosing pulmonary TB. However, for extrapulmonary TB and children, specific recommendations are only provided for Xpert® MTB/RIF, and Xpert® Ultra data for all other tests were limited when the review was conducted. Nevertheless, Xpert® Ultra has higher sensitivity in these groups, and trace positives are considered positive for these populations. Further details on the WHO-recommended diagnostic tools should be consulted in the latest TB consolidated guidelines and operational handbook on diagnostics (42,45).

Molecular WHO-recommended rapid diagnostic tests

Data from the individual participant data analysis found that 94% of medical inpatients had a positive WHO-recommended four-symptom screen, with a specificity of 11%. Thus, the difference in accuracy was minimal between the full screening and diagnostic strategy of using the WHO-recommended four-symptom screen followed by molecular WHO-recommended rapid diagnostic tests and using molecular WHO-recommended rapid diagnostic tests alone. WHO therefore recommends that medical inpatients be screened and tested with a molecular WHO-recommended rapid diagnostic test, regardless of symptoms, to inform a decision about whether to treat for TB. A 10% threshold TB prevalence among hospital inpatients living with HIV is recommended, considering the TB prevalence among the participants studied and striking a balance between ensuring rapid diagnosis in this critically ill population and the need to avoid overtreatment.

Because of the increased sensitivity of molecular WHO-recommended rapid diagnostic tests, but considering the likely challenges relating to access, high costs and feasibility in many countries, molecular WHO-recommended rapid diagnostic tests are also recommended as an option for screening for TB disease among all adults and adolescents living with HIV who are not medical inpatients in settings where the TB prevalence exceeds 10%. In this case, and as with all screening tools, a positive molecular WHO-recommended rapid diagnostic test screen should be followed by a diagnostic assessment to prevent the potential harm of overtreatment. In addition, due consideration should be made to giving priority to molecular WHO-recommended rapid diagnostic tests as a diagnostic test for all people with presumptive TB before scaling up molecular WHO-recommended rapid diagnostic tests as a screening test.

Table 6.3

WHO-recommended rapid diagnostic tests as initial tests for the diagnosis of TB.

Implementation considerations

Countries should position the WHO-recommended four-symptom screen, C-reactive protein, chest X-ray and molecular WHO-recommended rapid diagnostic tests in combination with diagnostic evaluation using molecular WHO-recommended rapid diagnostic tests and LF-LAM within national TB screening and diagnostic algorithms according to their feasibility, the level of the health facility, resources and equity. Although all the screening tools presented are recommended for all people living with HIV, evidence showed notable accuracy of C-reactive protein for TB screening for people not yet receiving ART and that chest X-ray enhanced the sensitivity of the WHO-recommended four-symptom screen among people receiving ART, both of which might be considered when choosing algorithms. Among inpatients in medical wards in settings with a high TB burden, evidence showed that the WHO-recommended four-symptom screen, C-reactive protein and chest X-ray had limited accuracy because of either extremely low specificity or suboptimal sensitivity and that using molecular WHO-recommended rapid diagnostic tests as an upfront screening and diagnostic test is warranted, particularly given the urgency of timely diagnosis in this population.

Data from the WHIP3TB trial highlight the need to conduct more intensified screening in addition to the WHO-recommended four-symptom screen. Programmes might consider using additional screening tools at the time of initial diagnosis of HIV or during the first antenatal care visit for pregnant women and then annually thereafter. To reduce the burden on the person living with HIV, such screening should be aligned with other routine HIV care visits, such as those for viral load monitoring or for ruling out TB disease before initiating TB preventive treatment, depending on the setting and the national guidelines on HIV. Where applicable, the WHO-recommended four-symptom screen should also be conducted as part of a comprehensive clinical evaluation and to inform the need for increased infection control and for other diagnostic tests, such as LF-LAM. Otherwise screening with the WHO-recommended four-symptom screen alone should be carried out during all other interactions between patients and health-care workers.

Consideration should also be given to the added benefit of including C-reactive protein for ruling out TB disease before initiating TB preventive treatment among people living with HIV. In a setting of 1% TB prevalence, among 1000 outpatients screened with the WHO-recommended four-symptom screen followed by C-reactive protein, 742 would be true negatives and eligible for TB preventive treatment versus only 416 found eligible by the WHO-recommended four-symptom screen. Similar to the case for using chest X-ray for ruling out TB disease before initiating TB preventive treatment, restricted access to C-reactive protein or chest X-ray should not be a barrier to initiating TB preventive treatment. When using a molecular WHO-recommended rapid diagnostic tests as a TB screening tool among people living with HIV is considered, it should be ensured that universal access to molecular WHO-recommended rapid diagnostic tests for everyone with presumptive TB is achieved first. The use of a molecular WHO-recommended rapid diagnostic test as a screening tool requires significant resources for implementation, including increasing the capacity of diagnostic networks and expanding sample transport networks. Depending on the feasibility and resources available, countries may choose to give priority to TB screening using molecular WHO-recommended rapid diagnostic tests among certain subpopulations, such as all medical inpatients, people with advanced disease or pregnant women living with HIV.

To inform programming and resource planning, countries are encouraged to monitor and evaluate the yield of TB screening among people living with HIV, disaggregated by screening tool. Additionally, more data are needed on the effectiveness, cost–effectiveness, feasibility and acceptability, frequency and optimal periodicity of routine, regular screening with the WHO-recommended four-symptom screen, C-reactive protein, chest X-ray and molecular WHO-recommended rapid diagnostic tests among people living with HIV. More studies are needed that explore the optimal placement of molecular WHO-recommended rapid diagnostic tests for screening in antenatal care settings versus within ART clinics. Lastly, more research is needed on the potential for screening people living with HIV with molecular WHO-recommended rapid diagnostic tests using specimens other than sputum.

Extrapulmonary TB among people living with HIV

The risk of extrapulmonary TB is higher among people living with HIV, especially those with lower CD4 cell counts. People living with HIV with extrapulmonary TB often have disseminated disease and are at high risk of rapid clinical deterioration and death. The commonest forms include lymph node (especially in the neck or under the arms), pleural (usually one-sided pleural effusion) and disseminated TB (disease that is not limited to one site in the body). Pericardial and meningeal TB are less frequent forms of extrapulmonary TB but are more likely to result in fatal outcomes (46). The diagnosis of extrapulmonary TB is challenging. Lack of pulmonary findings is not uncommon among people living with HIV with advanced immunosuppression, and disseminated TB can manifest as non-specific febrile illness. Extrapulmonary TB can be suspected among all people living with HIV presenting with TB symptoms. Further, symptoms suggesting specific organ involvement, such as breathlessness (pleural effusion or pericarditis), enlarged glands in the neck or armpit (lymphadenitis) and chronic headache or altered mental status (meningitis) should prompt further investigation for extrapulmonary TB (42). Bacterial confirmation is often difficult because of low sensitivity of smear microscopy and difficulty in obtaining samples from extrapulmonary sites. If possible, extrapulmonary specimens should be obtained. For people with suspected TB meningitis, a molecular WHO-recommended rapid diagnostic test is the preferred initial diagnostic test for cerebrospinal fluid (42). If lymphadenitis is suspected, molecular WHO-recommended rapid diagnostic tests may be used to test for samples obtained from lymph node biopsies or fine-needle aspiration. LF-LAM may also assist in the diagnosis because these people living with HIV are likely to have low CD4 cell counts (25). The accurate diagnosis of extrapulmonary TB is complex and difficult, especially in peripheral health facilities with limited support and diagnostic infrastructure.

6.5. Hepatitis B and C

6.5.3. Managing HIV and HCV coinfection

The global response and opportunities for eliminating HCV infection have been transformed by the introduction of curative, short-course direct-acting antiviral therapy, the widespread availability of rapid diagnostic testing for HCV antibody, the availability of NAT for HCV viraemia and the 2018 updated WHO recommendation of a “treat-all” approach regardless of stage of disease using three pangenotypic regimens (see Box 6.3) (74). This is further supported by a simplified public health approach for HCV testing and treatment and good practice principles of decentralization, integration and task sharing to promote the scale-up of testing and treatment.

In general, clinical stabilization of HIV disease with ART is advisable before starting treatment for HCV, especially for people with advanced immunosuppression (CD4 count below 200 cells/mm³). HCV treatment outcomes with direct-acting antiviral therapy are comparable for people with HIV and HCV coinfection to those solely infected with HCV (75). Because direct-acting antiviral therapy is safe and effective for people with HIV and HCV, they no longer need to be considered as a special or difficult-to-treat population (80). However, pangenotypic HCV regimens and ART have important drug–drug interactions. Checking for drug–drug interactions between HIV and HCV medications is therefore important.

Box 6.3Pangenotypic regimens currently available for adults 18 years and older

For adults without cirrhosis, the following pangenotypic regimens can be used:

• sofosbuvir + velpatasvir for 12 weeks
• sofosbuvir + daclatasvir for 12 weeks
• glecaprevir + pibrentasvir for 8 weeks.^a

For adults with compensated cirrhosis, the following pangenotypic regimens can be used:

• sofosbuvir + velpatasvir for 12 weeks
• glecaprevir + pibrentasvir for 12 weeks^a
• sofosbuvir + daclatasvir for 24 weeks
• sofosbuvir + daclatasvir for 12 weeks.^b

a

People with HCV genotype 3 infection who have received interferon and/or ribavirin in the past should be treated for 16 weeks.

b

May be considered in countries where the genotype distribution is known and the genotype 3 prevalence is <5%.

Pretreatment evaluation

Women of childbearing age may be offered pregnancy testing and be informed about the lack of available data on the safety and efficacy of direct-acting antiviral therapy during pregnancy. In addition, WHO recommends an alcohol intake assessment before initiating treatment and a fibrosis assessment using non-invasive tests such as the AST to platelet ratio index score or FIB-4 test to determine whether there is cirrhosis (66,74). This information will allow clinicians to decide on the appropriate treatment duration of the pangenotypic regimen of their choice based on the absence or presence of cirrhosis. The treatment duration of the recommended pangenotypic regimens sofosbuvir + daclatasvir and glecaprevir + pibrentasvir depends on the absence or presence of cirrhosis (Box 6.3 and Fig. 5.1).

The association between recommended pangenotypic regimens and EFV is either contraindicated (for sofosbuvir + velpatasvir and glecaprevir + pibrentasvir) or requires dose adjustment (for sofosbuvir + daclatasvir). Chapter 4 includes a summary of the drug–drug interactions between WHO-recommended HIV ARV drugs and HCV drugs as do the annexes. Where drug–drug interactions are likely, ARV drug substitutions may be considered before initiating HCV therapy. Prescribers may consult the University of Liverpool webpage on hepatitis drug interactions (81) before prescribing, since the details of interactions are frequently updated. This website includes details of interactions with prescribed and non-prescribed medicines.

Fig. 6.1

Algorithm for the diagnosis, treatment and monitoring of chronic HCV infection among adults and adolescents. ^a People with HCV genotype 3 infection who have received interferon and/or ribavirin in the past should be treated for 16 weeks. ^b May be considered (more...)

6.5.5. Preventing mother-to-child transmission of HBV infection

Among people living with HIV, HBV coinfection is associated with a higher rate of HBV e-antigen positivity, higher HBV viraemia and increased perinatal transmission of perinatal HBV infection (13). Eliminating HBV infection as a public health threat requires reducing HBsAg prevalence to less than 0.1% among children five years old. This can be achieved by universally immunizing newborns against HBV and other interventions to prevent the mother-to-child transmission of HBV. The 2020 WHO guidelines on antiviral prophylaxis for hepatitis B in pregnancy (76) included the following recommendations.

• Routinely testing pregnant women for HIV, HBV and syphilis. All pregnant women should be tested for HIV, syphilis and HBsAg at least once and as early as possible in the pregnancy (HIV standing recommendation since 2007; syphilis: strong recommendation, moderate-certainty evidence; HBsAg: strong recommendation, low-certainty evidence).
• Existing recommendations on immunization from the WHO position paper (80). All infants should receive their first dose of HBV vaccine as soon as possible after birth, preferably within 24 hours. Delivery of HBV vaccine within 24 hours of birth should be a performance indicator for all immunization programmes, and reporting and monitoring systems should be strengthened to improve the quality of data on the birth dose. The birth dose should be followed by two or three doses to complete the primary series.
• Tenofovir prophylaxis to prevent mother-to-child transmission of HBV. Women coinfected with HIV and HBV should be receiving TDF-based ART, which will provide prophylaxis to prevent the mother-to-child transmission of HBV. This is in addition to three-dose HBV vaccination for all infants, including timely birth dose (conditional recommendation, moderate-certainty evidence).

Table 6.4

Summary of recommendations on testing for chronic HBV and HCV infection.

6.6. Malaria

6.7. Buruli ulcer

6.8. Leishmaniasis

6.9. Cervical cancer

Supporting evidence

Systematic literature reviews were conducted for the effects of interventions (including tests) on outcomes, and for the accuracy of screening tests in the general population and among women living with HIV. An individual-patient data meta-analysis was performed to analyse age-specific data for cervical cancer and cervical intraepithelial neoplasia among women living with HIV.

A mathematical model, Policy1-Cervix, was also used to estimate the risk of important outcomes of the priority screening and treatment strategies across 78 low- and middle-income countries (122–124). A separate model for cervical cancer among women living with HIV in the United Republic of Tanzania was used to evaluate outcomes for women living with HIV (125). Outcomes were assessed over the lifetime of birth cohorts eligible for screening in 2030 onwards and included cervical cancer incidence and mortality, precancer treatment and additional preterm deliveries as a result of precancer treatment.

Women and girls 15 years and older, regardless of their previous cervical cancer screening or treatment status, were invited to participate in an anonymous, voluntary survey. The survey was promoted through the Union for International Cancer Control and the WHO advisory and advocacy groups for women living with HIV and shared through WHO regional focal points for cervical cancer elimination initiative.

Table 6.5

Summary of WHO screening and treatment recommendations to prevent cervical cancer for women living with HIV.

Good practice statement for the general population and women living with HIV

Once a decision to treat a woman is made, treating as soon as possible within six months is good practice to reduce losses to treatment. However, for women who are pregnant, good practice includes deferral until after pregnancy.

In circumstances when treatment is not provided within this time frame, evaluating the woman before treatment is good practice.

Recommendation

WHO suggests large loop excision of the transformation zone or cold-knife conization for women who have histologically confirmed adenocarcinoma in situ.

Remarks: Loop excision may be preferred for women of reproductive age, in settings with greater availability of large loop excision of the transformation zone and by providers with greater expertise performing large loop excision of the transformation zone. Cold-knife conization may be preferred when interpretation of the margins of the histological specimen is imperative. (Conditional recommendation, low-certainty evidence).

Source: Guidelines for screening and treatment of precancerous lesions for cervical cancer prevention: WHO guidelines (126).

6.10. Noncommunicable diseases

6.11. Mental health among people living with HIV

6.12. Drug use and drug use disorders

People who use drugs may experience a range of disorders related to drug use, including drug dependence, intoxication, withdrawal and overdose. Injecting drug use is associated with a range of diseases and infections, including HIV, viral hepatitis, TB, septicaemia and bacterial endocarditis.

WHO, UNODC and UNAIDS recommend a comprehensive package of interventions for HIV prevention, treatment and care for people who inject drugs, including needle and syringe programmes, opioid substitution therapy, HIV testing and counselling, ART, preventing and treating sexually transmitted infections, condom programmes, targeted behaviour change communication, preventing and treating viral hepatitis and preventing, diagnosing and treating TB. More recently, WHO updated this package to include community distribution of naloxone to manage opioid overdose as well as a set of enabling interventions to overcome the structural barriers for people who use drugs and other key populations to access these health interventions. These enabling interventions include revising laws and legislation that criminalize the consumption and possession of drugs and address violence, stigma and discrimination in health-care settings.

Although the focus with HIV has been injecting opioids, a link is becoming more evident between using other drugs such as amphetamine-like stimulants and sexual risk and transmission of HIV (214).

A form of sexualized drug use is also seen in subgroups of men who have sex with men, often referred to as chemsex, with increased risk of HIV and sexually transmitted infections, including HCV transmission.

6.13. Sexually transmitted infections

6.14. Vaccines for people living with HIV

Immunizations are an important component of the HIV care package in many international guidelines, and people living with HIV should be assessed for eligibility for vaccination at all stages of care (235–237). Vaccines usually have better safety and efficacy among people living with HIV who are receiving ART and those without significant immunosuppression, notably when the CD4 cell count is above 200 cells/mm³. People with more severe immunosuppression may be at higher risk of complications from some live attenuated vaccines. Inactivated vaccines, although safe, can be less effective among these people and may require supplemental doses or revaccination after ART-induced immune reconstitution. Transient increases in plasma HIV-RNA load have also been reported after the administration of several vaccines. Available evidence indicates that these transient increases are not clinically significant (238,239).

In general, HIV-exposed infants, children and adolescents with HIV should receive all vaccines under routine vaccination according to recommended national immunization schedules (240,241).

COVID-19 vaccination

Many of the COVID-19 vaccine studies have included a few people living with HIV in their trials. Despite limited data, the available information suggests that current WHO-recommended COVID-19 vaccines are safe for people living with HIV (242). No interactions have been reported between COVID-19 vaccines and ARV drugs, which people living with HIV should continue to take after vaccination to maintain health.

The source of most recommendations for vaccinating people living with HIV is WHO position papers and summary tables published in 2017 and 2018 (80,127,243–254). The position papers include guidance on BCG, HPV, HBV, measles, dengue, rubella, typhoid, pneumococcal and cholera vaccination for people living with HIV (Table 6.6).

Table 6.6

HIV-specific guidance for selected vaccines from WHO vaccine position papers.

Further information on other vaccinations comes from a scoping review (255) that aims to identify and evaluate new evidence on using selected vaccines for children living with HIV concerning vaccine safety, efficacy, dosing and immunization schedule together with the effect of immune status and ART at the time of vaccination.

The scoping review for children living with HIV sought to identify safety and efficacy studies published since the last published systematic review (2012) of immunization of children living with HIV (254). The final scoping review included 19 articles.

The scoping review focused on:

• vaccines recommended for all children: diphtheria, tetanus, oral polio, pertussis, Haemophilus influenzae type B, rotavirus, pneumococcal conjugate and rubella;
• vaccines recommended for children in some high-risk populations: dengue, rabies, typhoid, meningococcal and hepatitis A;
• vaccines for children receiving vaccinations from immunization programmes with certain characteristics: varicella, influenza and mumps; and
• vaccines for children residing in certain regions: Japanese encephalitis, tick-borne encephalitis and yellow fever.

None of the studies assessing safety showed any significant difference in side-effects among children living with HIV compared with uninfected controls. Although in most of the studies, children living with HIV had lower antibody levels in response to vaccination, the proportion of children reaching the seroprotective levels was similar compared with uninfected children for most of the vaccines, except for pertussis vaccine and oral polio vaccine, for which children living with HIV reached lower levels. Eight of the 17 included studies had a sample size of 50 or fewer children living with HIV, most of whom were receiving ART.

Immunization against some diseases such as influenza, HBV, pneumococcal disease and tetanus is frequently indicated for adults living with HIV. Other immunizations may be recommended based on age, risk factors or travel plans.

For currently recommended vaccination schedules and detailed guidance on immunization for all age groups, see WHO recommendations for routine immunization – summary tables (254).

WHO has position papers on each vaccine and statements about them for people living with HIV (243–253).

6.15. HIV-related skin and oral conditions

HIV infection increases the prevalence and severity of skin and oral diseases, especially when the person’s CD4 cell count declines below 200 cells/mm³. As a result, skin and oral conditions affect up to 90% of adults and children with HIV in resource-limited settings (51). Adverse drug reactions of the skin are also 100 times more common among people living with HIV than among the general population, and their prevalence increases as immunodeficiency worsens. Immune reconstitution inflammatory syndrome occurs in 10–25% of people living with HIV starting ART. Cutaneous manifestations of immune reconstitution inflammatory syndrome, such as seborrhoeic dermatitis, anogenital herpes, acne, tinea, folliculitis, Kaposi’s sarcoma, herpes zoster, genital warts, molluscum contagiosum and pityriasis versicolor, are common, occurring among up to 50% of people living with HIV commencing ART with a low CD4 cell count (256).

Skin and oral manifestations of HIV infection can aggravate stigma in some societies as physical signs in the form of skin diseases, such as papular pruritic eruption, that suggest the possibility of HIV infection could make the affected person more vulnerable to discrimination (51).

WHO guidelines (257) describe common HIV-related skin disorders based on the burden of disease among adults and children living with HIV and the availability of evidence and effective interventions. These are Kaposi’s sarcoma, seborrhoeic dermatitis, papular pruritic eruption, eosinophilic folliculitis, tinea infections, herpes zoster, scabies, molluscum contagiosum, oropharyngeal candidiasis, Stevens-Johnson syndrome and toxic epidermal necrolysis.

Certain systemic diseases, such as Kaposi’s sarcoma, may initially be noted on the skin and may require urgent ART to reduce mortality. Others, while not always a major cause of mortality, can be a source of severe morbidity through, for example, itching that provokes scratching, secondary infections, disfigurement, sleep disturbance and mental stress. Candidiasis can cause pain on swallowing, limiting a person’s ability to take ARV drugs.

Because of a lack of services to promptly diagnose and manage skin and oral conditions, many people attempt to conceal the skin disease or avoid social contact. These could affect their health-seeking behaviour, negatively affecting their self-esteem and quality of life. Skin and oral conditions are one of the most common management problems faced by health-care workers caring for people living with HIV.

In 2014, WHO released guidelines for treating common HIV-associated skin and oral conditions in low- and middle-income countries (257). They are applicable for all adults, pregnant women, adolescents and children living with HIV and recommend HIV testing for everyone with unknown HIV status presenting with the discussed skin conditions, and if the HIV status is known, they should be evaluated to initiate ART.

ART is the initial treatment of choice for several of these conditions, such as Kaposi’s sarcoma, papular pruritic eruption, eosinophilic folliculitis and molluscum contagiosum.

6.16. Nutritional care and support

Low energy intake combined with increased energy demands from HIV infection (258–260) and related opportunistic and other infections may lead to HIV-related weight loss and wasting. In addition, an altered metabolism, reduced appetite and higher incidence of diarrhoea may lower nutrient intake and absorption and lead to nutrient losses. These effects may all be compounded in low-income, food-insecure contexts. Low body mass (BMI less than 18.5 kg/m² for adults), weight loss and wasting in children are all independent risk factors for HIV disease progression and mortality (261,262). Nutritional assessment (anthropometry, clinical and dietary assessment), counselling and support should be an integral component of HIV care and conducted at enrolment in care and monitored across the care continuum. Malnourished people with HIV, especially in food-insecure contexts, may require food supplements in addition to ART to support nutritional recovery. Weight loss or failure to regain or maintain a healthy weight at any stage of HIV infection, including while receiving ART, should trigger further assessment and appropriate interventions.

6.17. Palliative care

6.18. Noncommunicable diseases among children and adolescents

As access to treatment improves, children and adolescents living with HIV receiving ART should have the chance to have an improved quality of life and reach their full potential. Service delivery platforms need to plan how to implement this, since screening for chronic comorbidities and disabilities, neural development and growth delays, promoting nurturing care and supporting the mental development of children and adolescents as they age are of paramount importance.

Worldwide, 530 000 children five years and younger are living with HIV, and 5.4 million children five years and younger are HIV-exposed and uninfected (328).

The early years lay a foundation for health, well-being and productivity that lasts throughout childhood, adolescence and adulthood (329). Failure to meet children’s needs in this critical window limits their ability to achieve their full developmental potential. Children living with HIV may be especially vulnerable during this period because of the following risk factors:

• being born small for gestational age or prematurely (330);
• having more severe pneumonia, diarrhoeal disease and exposure to TB (331);
• receiving suboptimal breastfeeding and nutrition, resulting in poor growth;
• being cared for by a mother or other caregiver who is experiencing health challenges, both physically and mentally;
• being excluded from opportunities to interact with other children, adults and their surroundings;
• being raised in extreme poverty or exposed to violence; and
• being exposed to maternal HIV and to ARV medicine, resulting in worse developmental outcomes compared with their non-HIV-affected peers.

Enabling young children to achieve their full developmental potential is a human right and an essential requisite for sustainable development. Given the critical importance of enabling children to make the best start in life, the health sector, among other sectors, has an important role and responsibility to support nurturing care for early childhood development. WHO has produced Improving early childhood development: WHO guideline (332), which provides direction for strengthening policies and programmes to better address early childhood development.

The family primarily provides the nurturing care that children need to develop in the earliest years. Many parents and other caregivers need support to put this into practice. The guideline contains four recommendations for caregivers, health professionals and other workers who can assist them as well as policy-makers and other stakeholders. The recommendations relate to (1) providing responsive care and activities for early learning during the first three years of life; (2) including responsive care and early learning as part of interventions for optimizing the nutrition of infants and young children; and (3) integrating psychosocial interventions to support maternal mental health into early childhood health and development services (332).

To reach their full potential, children need the five interrelated components of nurturing care: good health, adequate nutrition, safety and security, responsive caregiving and opportunities for early learning. This begins in pregnancy and continues throughout the life-course. Adding a nurturing care lens to routine maternal, newborn and child health and HIV prevention and care services can improve the quality of the engagement between health-care workers and caregivers (334) (Fig. 6.3).

Fig. 6.3

Adding a nurturing care lens to maternal, newborn and child health and HIV prevention services (334).

Service delivery

Various service delivery platforms already established could be used to screen for and manage noncommunicable diseases among children at different stages of their lives. For children younger than five years, examples include early childhood development, under-five clinics and HIV services. For children 5–9 years old, examples include integrated school and HIV services. For adolescents 10–19 years old, examples include adolescent-friendly services. Although implementing screening and prevention of noncommunicable diseases or comorbidities presents many challenges, opportunities to integrate this kind of care into existing adolescent activities are numerous. Some clinics have already established adolescent groups to address various health issues (354). HIV is one of the only conditions that results in an adolescent population interacting regularly with the health system. This should be leveraged to integrate a more comprehensive approach to health. Table 6.7 summarizes the platforms, screening approaches, tools needed and interventions that are applicable across young children, children of school age and adolescents.

Comprehensive HIV care for children and adolescents includes:

• earlier initiation of ART to prevent complications:
• monitoring growth and musculoskeletal and neurocognitive development;
• screening for heart, lung, kidney and neurocognitive disease;
• assessing psychosocial status (schooling and guardianship) and mental health;
• managing common mental health disorders and providing psychosocial support;
• optimizing nutrition;
• catching up or revaccinating according to WHO guidelines, such as pneumococcal and influenza vaccination;
• HPV vaccination for adolescents;
• cervical cancer screening after sexual debut;
• referring to clinical specialties for management if feasible;
• liaising with disability and rehabilitation services;
• school-based programmes to provide educational support;
• leveraging existing early child development platforms for supporting children living with HIV; and
• linking to community-based psychosocial support services.

Table 6.7

Service Delivery: Potential ways to integrate screening and possible interventions.

Additional resources relating to Chapter 6

• Comprehensive cervical cancer control: a guide to essential practice. 2nd ed. Geneva: World Health Organization; 2014 (https://apps​.who.int​/iris/handle/10665/144785). [PubMed: 25642554]
• WHO guidelines for treatment of cervical intraepithelial neoplasia 2–3 and adenocarcinoma in situ: cryotherapy, large loop excision of the transformation zone, and cold knife conization. Geneva: World Health Organization; 2014 (https://apps​.who.int​/iris/handle/10665/104174). [PubMed: 24901204]
• Human papillomavirus vaccines: WHO position paper, May 2017. Wkly Epidemiol Rec. 2017;92:241–268 (https://apps​.who.int​/iris/handle/10665/255354). [PubMed: 28530369]
• WHO guidance note: comprehensive cervical cancer prevention and control: a healthier future for girls and women. Geneva: World Health Organization; 2013 (https://apps​.who.int​/iris/handle/10665/78128).
• Use of cryotherapy for cervical intraepithelial neoplasia: evidence base. Geneva: World Health Organization; 2011 (https://apps​.who.int​/iris/handle/10665/70855). [PubMed: 23741775]
• Package of essential noncommunicable (PEN) disease interventions for primary health care in low-resource settings. Geneva: World Health Organization; 2010 (https://apps​.who.int​/iris/handle/10665/44260).
• Prevention and control of noncommunicable diseases: guidelines for primary health care in low-resource settings. Geneva: World Health Organization; 2012 (https://apps​.who.int​/iris/handle/10665/76173). [PubMed: 23844451]
• Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations, 2016 update. Geneva: World Health Organization; 2016 (https://apps​.who.int​/iris/handle/10665/246200). [PubMed: 27559558]
• WHO, UNODC, UNAIDS. WHO, UNODC and UNAIDS technical guide for countries to set targets for universal access to HIV prevention, treatment and care for injecting drug users. Geneva: World Health Organization; 2012 (https://apps​.who.int​/iris/handle/10665/44068).
• Community management of opioid overdose. Geneva: World Health Organization; 2014 (https://apps​.who.int​/iris/handle/10665/137462). [PubMed: 25577941]
• Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. Geneva: World Health Organization; 2009 (https://apps​.who.int​/iris/handle/10665/43948). [PubMed: 23762965]
• Guidance on prevention of viral hepatitis B and C among people who inject drugs. Geneva: World Health Organization; 2012 (https://apps​.who.int​/iris/handle/10665/75357). [PubMed: 23805439]
• Integrating collaborative TB and HIV services within a comprehensive package of care for people who inject drugs: consolidated guidelines. Geneva: World Health Organization; 2016 (https://apps​.who.int​/iris/handle/10665/204484).
• HIV prevention, treatment, care and support for people who use stimulant drugs. Vienna: United Nations Office on Drugs and Crime; 2019 (https://www​.unodc.org​/documents/hiv-aids​/publications/People_who_use_drugs​/19-04568​_HIV_Prevention_Guide_ebook.pdf).
• Guidelines for the management of symptomatic sexually transmitted infections. Geneva: World Health Organization; in press.
• WHO guidelines for the treatment of Neisseria gonorrhoeae. Geneva: World Health Organization; 2016 (https://apps​.who.int​/iris/handle/10665/246114). [PubMed: 27512795]
• WHO guidelines for the treatment of Chlamydia trachomatis. Geneva: World Health Organization; 2016 (https://apps​.who.int​/iris/handle/10665/246165). [PubMed: 27559553]
• WHO guidelines for the treatment of Treponema pallidum (syphilis). Geneva: World Health Organization; 2016 (https://apps​.who.int​/iris/handle/10665/249572). [PubMed: 27631046]
• WHO guidelines for the treatment of genital herpes simplex virus. Geneva: World Health Organization; 2016 (https://apps​.who.int​/iris/handle/10665/250693). [PubMed: 27875039]
• WHO guidelines on syphilis screening and treatment for pregnant women. Geneva: World Health Organization; 2017 (https://apps​.who.int​/iris/handle/10665/259003). [PubMed: 29757595]
• Prevention and treatment of HIV and other sexually transmitted infections among men who have sex with men and transgender people: recommendations for a public health approach. Geneva: World Health Organization; 2011 (https://apps​.who.int​/iris/bitstream/handle​/10665/44619/9789241501750_eng.pdf). [PubMed: 26158187]
• Prevention and treatment of HIV and other sexually transmitted infections for sex workers in low- and middle-income countries: recommendations for a public health approach. Geneva: World Health Organization; 2012 (https://apps​.who.int​/iris/handle/10665/77745). [PubMed: 26131541]
• Consolidated guidelines on HIV testing services, 2019. Geneva: World Health Organization; 2020 (https://apps​.who.int​/iris/handle/10665/336323).
• Dual HIV/syphilis rapid diagnostic tests can be used as the first test in antenatal care: policy brief. Geneva: World Health Organization; 2019 (https://apps​.who.int​/iris/handle/10665/329965).
• Brief sexuality-related communication: recommendations for a public health approach. Geneva: World Health Organization; 2015 (https://apps​.who.int​/iris/handle/10665/170251). [PubMed: 26290928]

Violence against women

• Responding to children and adolescents who have been sexually abused: WHO clinical guidelines. Geneva: World Health Organization; 2017 (https://apps​.who.int​/iris/handle/10665/259270). [PubMed: 29630189]
• Strengthening health systems to respond to women subjected to intimate partner violence or sexual violence: a manual for health managers. Geneva: World Health Organization; 2015 (https://apps​.who.int​/iris/handle/10665/259489).
• Responding to intimate partner violence and sexual violence against women: WHO clinical and policy guidelines. Geneva: World Health Organization; 2013 (https://apps​.who.int​/iris/handle/10665/85240). [PubMed: 24354041]

Sexual and reproductive health guidelines for women living with HIV

• WHO, UNFPA. Sexual and reproductive health of women living with HIV/AIDS. Guidelines on care, treatment and support for women living with HIV/AIDS and their children in resource-constrained settings. Geneva: World Health Organization; 2006 (https://apps​.who.int​/iris/handle/10665/43473).
• Consolidated guideline on sexual and reproductive health and rights of women living with HIV. Geneva: World Health Organization; 2017 (https://apps​.who.int​/iris/handle/10665/254885). [PubMed: 28737847]

Nutrition and HIV

• Essential nutrition actions: mainstreaming nutrition through the life-course. Geneva: World Health Organization; 2019 (https://apps​.who.int​/iris/handle/10665/32626).
• HIV and infant feeding in emergencies: operational guidance: the duration of breastfeeding and support from health services to improve feeding practices among mothers living with HIV. Geneva: World Health Organization; 2018 (https://apps​.who.int​/iris/handle/10665/272862). [PubMed: 27583316]
• Updates on HIV and infant feeding: the duration of breastfeeding, and support from health services to improve feeding practices among mothers living with HIV. Geneva: World Health Organization; 2016 (https://apps​.who.int​/iris/handle/10665/44384). [PubMed: 27583316]

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Footnotes

1

Site-specific cancers: bladder, breast, colon, endometrial, oesophageal adenocarcinoma, gastric and renal.

2

A person living with HIV is classified as seriously ill if one or more of the following danger signs are present: unable to walk unaided; respiratory rate over 30 per minute; fever of more than 39°C; or pulse rate exceeding 120 per minute.