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This second edition of the book provides up-to-date information on new drugs, new proven HIV prevention interventions, a new chapter on positive prevention, and current HIV epidemiology. This definitive text covers all aspects of HIV/AIDS in South Africa, from basic science to medicine, sociology, economics and politics. It has been written by a highly respected team of South African HIV/AIDS experts and provides a thoroughly researched account of the epidemic in the region.

HIV/AIDS is a catastrophe globally but nowhere more so than in sub-Saharan Africa, which in 2008 accounted for 67 percent of cases worldwide and 91 percent of new infections.The Institute of Medicine recommends that the United States and African nations move toward a strategy of shared responsibility such that these nations are empowered to take.

Evidence suggests that person-centered care (PCC) has the potential to overcome inequities in access to HIV services, support quality care that is responsive to diverse needs while increasing efficiencies and resilience of the health system. Despite emerging evidence on the effectiveness of PCC, there is limited information available on how to assess it in diverse clinical settings. This work builds upon a systematic literature review published elsewhere by this study team to develop a PCC framework for HIV treatment service delivery. The PCC framework informed the development of the PCC assessment tool (PCC-AT) to assess the degree to which PCC activities are operationalized in diverse HIV treatment settings. The study objectives are to assess: (1) content validity of the PCC framework; (2) PCC-AT score consistency and reliability between health facility staff and clients; and (3) PCC-AT feasibility in HIV treatment settings. The study team will pilot the PCC-AT among staff in five health facilities and conduct subsequent focus group discussions (FGDs) to determine PCC-AT feasibility. Key informant interviews (KIIs) with clients will explore content validity among PLHIV relative to each subdomain of the PCC-AT and provide a basis to compare score concordance. Quantitative data among health facility staff will examine how many and which cadres participated in the PCC-AT pilot and FGD, years of experience, gender, and the time required to complete the PCC-AT. Information on clients will include total time accessing treatment at the study health facility, years since diagnosis, age and gender. Qualitative data analysis, using descriptive coding with NVivo or a similar software, will be drawn from transcripts from the PCC-AT pilots, FGDs and KIIs. PCC assessment is a novel approach that aims to help health facilities assess and strengthen their ability to deliver PCC services to improve client outcomes.

The benefits of combination antiretroviral therapy (cART) for HIV replication and transmission control have led to its universal recommendation. Many people living with HIV are, however, still undiagnosed or diagnosed late, especially in sub-Saharan Africa, where the HIV disease burden is highest. Further expansion in HIV treatment options, incorporating women-centred approaches, is essential to make individualised care a reality. With a longer life expectancy than before, people living with HIV are at an increased risk of developing non-AIDS comorbidities, such as cardiovascular diseases and cancers. Antiretroviral strategies are evolving towards a decrease in drug burden, and some two-drug combinations have proven efficacy for maintenance therapy. Investigational immune checkpoint inhibitors and broadly neutralising antibodies with effector functions have energised the HIV cure research field as the search for an effective vaccine continues. In this Seminar, we review advances and challenges relating to the goal of an AIDS-free world.

Few evidence-based interventions have been widely adopted in common clinical settings, particularly for opioid-dependent people with HIV (PWH) seeking drug treatment. We developed a brief evidence-based intervention, Holistic Health for HIV (3H+), specifically for ease of implementation and integration within drug treatment settings. In this study, we compared 3H+ to the gold standard, Holistic Health Recovery Program (HHRP+) using a non-inferiority trial. Between 2012 and 2017, 106 participants were randomly assigned to either the brief 3H+ intervention or the gold standard HHRP+. HIV treatment (ART adherence, viral suppression) and risk behaviors (sharing injection equipment, condom use) were compared between the two arms at baseline, end-of-intervention (EOI-12 weeks) and at follow-up (24 weeks). Average treatment effect was calculated based on the difference-in-difference (DID) estimator and a non-parametric bootstrap was used to assess non-inferiority. At the 12-week EOI point, 3H+ was found to be non-inferior to HHRP+ with respect to multiple outcomes: percent sharing syringes and needles (DID:1.4, 95%CI [-18.6,21.5], p<0.01) and attainment of high ART adherence (DID: 9.7, 95%CI: [-13.1, 32.2], p = 0.04). At the 24-week EOI point, 3H+ was found to be non-inferior to HHRP+ with respect to percent sharing syringes and needles (DID: 8.9, [-10.1, 28.30], p = 0.04) and attainment of viral suppression (DID: 18.9, 95% CI:[-7.1, 42.0], p = 0.01). For other indicators, such as consistent condom use, the hypothesis test for non-inferiority was inconclusive at the 12-week EOI (DID: -20.2, 95%CI [-48.9-10.7], p = 0.51). For HIV treatment as prevention to be effective, PWH need to achieve viral suppression. In the absence of this success, they must reduce HIV risk behaviors. The finding that 3H+ was non-inferior to HHRP+ suggests that brief behavioral interventions can be deployed in real world settings to help more efficiently achieve Ending the HIV Epidemic goals.

Few evidence-based interventions have been widely adopted in common clinical settings, particularly for opioid-dependent people with HIV (PWH) seeking drug treatment. We developed a brief evidence-based intervention, Holistic Health for HIV (3H+), specifically for ease of implementation and integration within drug treatment settings. In this study, we compared 3H+ to the gold standard, Holistic Health Recovery Program (HHRP+) using a non-inferiority trial. Between 2012 and 2017, 106 participants were randomly assigned to either the brief 3H+ intervention or the gold standard HHRP+. HIV treatment (ART adherence, viral suppression) and risk behaviors (sharing injection equipment, condom use) were compared between the two arms at baseline, end-of-intervention (EOI-12 weeks) and at follow-up (24 weeks). Average treatment effect was calculated based on the difference-in-difference (DID) estimator and a non-parametric bootstrap was used to assess non-inferiority. At the 12-week EOI point, 3H+ was found to be non-inferior to HHRP+ with respect to multiple outcomes: percent sharing syringes and needles (DID:1.4, 95%CI [-18.6,21.5], p<0.01) and attainment of high ART adherence (DID: 9.7, 95%CI: [-13.1, 32.2], p = 0.04). At the 24-week EOI point, 3H+ was found to be non-inferior to HHRP+ with respect to percent sharing syringes and needles (DID: 8.9, [-10.1, 28.30], p = 0.04) and attainment of viral suppression (DID: 18.9, 95% CI:[-7.1, 42.0], p = 0.01). For other indicators, such as consistent condom use, the hypothesis test for non-inferiority was inconclusive at the 12-week EOI (DID: -20.2, 95%CI [-48.9-10.7], p = 0.51). For HIV treatment as prevention to be effective, PWH need to achieve viral suppression. In the absence of this success, they must reduce HIV risk behaviors. The finding that 3H+ was non-inferior to HHRP+ suggests that brief behavioral interventions can be deployed in real world settings to help more efficiently achieve Ending the HIV Epidemic goals.

Antiretroviral therapy (ART), when taken consistently, reduces morbidity and mortality associated with human immunodeficiency virus and viral transmission. Suboptimal treatment adherence is associated with regimen complexity and high tablet burden. Single-tablet regimens (STRs) provide a complete treatment regimen in a single tablet. This study examined the relationship between STRs (vs multiple-tablet regimens [MTRs]), treatment adherence, and viral suppression. A systematic review was conducted to identify studies investigating at least one of the following: (1) STR/MTR use and adherence; (2) levels of adherence and viral suppression; and (3) STR/MTR use and viral suppression. Meta-analysis was performed to assess the relationship between STR vs MTR use and adherence in observational settings at ≥95% and ≥90% adherence thresholds. In total, 29 studies were identified across the three objectives; two studies were relevant for all objectives. STRs were associated with higher treatment adherence than MTRs in 10/11 observational studies: a 63% greater likelihood of achieving ≥95% adherence (95% CI=1.52-1.74; <0.001) and a 43% increase in the likelihood of achieving ≥90% adherence (95% CI=1.21-1.69; <0.001). Higher adherence rates were associated with higher levels of viral suppression in 13/18 studies. Results were mixed in five studies investigating the association between STR or MTR use and viral suppression. Although the direct effect of STRs vs MTRs on viral suppression remains unclear, this study provided a quantitative estimate of the relationship between STRs and ART adherence, demonstrating that STRs are associated with significantly higher ART adherence levels at 95% and 90% thresholds. Findings from the systematic review showed that improved adherence results in an increased likelihood of achieving viral suppression in observational settings. Future research should utilize similar measures for adherence and evaluate viral suppression to improve assessment of the relationship between pill burden, adherence, and viral suppression.

Despite receiving antiretroviral therapy, most patients with HIV still have latent reservoirs of the virus; here, these reservoirs are shown to be dominated by viruses with cytotoxic T lymphocyte escape mutations, with potential implications for the development of therapeutic vaccines. HIV-1 reservoirs analysed Antiretroviral therapy does not cure HIV-1 infection: despite drug treatment, most patients still have latent reservoirs of the virus. This study of immune cells isolated from 30 HIV-1-infected patients who had been on antiretroviral therapy for at least two years and had maintained undetectable plasma HIV-1 RNA levels, shows that these viral reservoirs are dominated by viruses with cytotoxic T lymphocyte escape mutations. This finding implies that future directions in therapeutic vaccine design may need to focus on boosting broad cytotoxic T lymphocyte responses. Despite antiretroviral therapy (ART), human immunodeficiency virus (HIV)-1 persists in a stable latent reservoir 1 , 2 , primarily in resting memory CD4 + T cells 3 , 4 . This reservoir presents a major barrier to the cure of HIV-1 infection. To purge the reservoir, pharmacological reactivation of latent HIV-1 has been proposed 5 and tested both in vitro and in vivo 6 , 7 , 8 . A key remaining question is whether virus-specific immune mechanisms, including cytotoxic T lymphocytes (CTLs), can clear infected cells in ART-treated patients after latency is reversed. Here we show that there is a striking all or none pattern for CTL escape mutations in HIV-1 Gag epitopes. Unless ART is started early, the vast majority (>98%) of latent viruses carry CTL escape mutations that render infected cells insensitive to CTLs directed at common epitopes. To solve this problem, we identified CTLs that could recognize epitopes from latent HIV-1 that were unmutated in every chronically infected patient tested. Upon stimulation, these CTLs eliminated target cells infected with autologous virus derived from the latent reservoir, both in vitro and in patient-derived humanized mice. The predominance of CTL-resistant viruses in the latent reservoir poses a major challenge to viral eradication. Our results demonstrate that chronically infected patients retain a broad-spectrum viral-specific CTL response and that appropriate boosting of this response may be required for the elimination of the latent reservoir.

Human immunodeficiency virus type 1 (HIV-1)-specific monoclonal antibodies with extraordinary potency and breadth have recently been described. In humanized mice, combinations of monoclonal antibodies have been shown to suppress viraemia, but the therapeutic potential of these monoclonal antibodies has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific monoclonal antibodies, as well as the single glycan-dependent monoclonal antibody PGT121, resulted in a rapid and precipitous decline of plasma viraemia to undetectable levels in rhesus monkeys chronically infected with the pathogenic simian–human immunodeficiency virus SHIV-SF162P3. A single monoclonal antibody infusion afforded up to a 3.1 log decline of plasma viral RNA in 7 days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa and lymph nodes without the development of viral resistance. Moreover, after monoclonal antibody administration, host Gag-specific T-lymphocyte responses showed improved functionality. Virus rebounded in most animals after a median of 56 days when serum monoclonal antibody titres had declined to undetectable levels, although, notably, a subset of animals maintained long-term virological control in the absence of further monoclonal antibody infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of monoclonal antibody therapy for HIV-1 in humans. Treatment of SHIV-infected monkeys with potent broadly neutralizing anti-HIV-1 monoclonal antibodies resulted in rapid control of viral replication in both peripheral blood and tissues; viral rebound was linked to decreasing antibody concentrations and not the generation of escape mutations, and setpoint viral load following viral rebound remained lower than the initial baseline viral load. Monoclonal antibodies in HIV therapy Two papers published this week test the new generation of broad and potent anti-HIV1 monoclonal antibodies (mAbs) in primate models with promising results, both concluding that their results strongly encourage the investigation of mAb therapy for HIV-1 in humans. Dan Barouch et al . show that a single infusion of the potent, broadly neutralizing anti-HIV-1 antibody PGT121, as well as various mAb cocktails, suppress the virus to undetectable levels in just a week in SHIV-infected rhesus monkeys. Masashi Shingai et al . report that co-administration of the antibodies 3BNC117 and 10-1074 results in potent suppression of plasma viraemia lasting for several weeks in chronically SHIV-infected macaques.