Highly active antiretroviral treatment for the prevention of HIV transmission

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Abstract

In 2007 an estimated 33 million people were living with HIV; 67% resided in sub-Saharan Africa, with 35% in eight countries alone. In 2007, there were about 1.4 million HIV-positive tuberculosis cases. Globally, approximately 4 million people had been given highly active antiretroviral therapy (HAART) by the end of 2008, but in 2007, an estimated 6.7 million were still in need of HAART and 2.7 million more became infected with HIV.

Although there has been unprecedented investment in confronting HIV/AIDS - the Joint United Nations Programme on HIV/AIDS estimates $13.8 billion was spent in 2008 - a key challenge is how to address the HIV/AIDS epidemic given limited and potentially shrinking resources. Economic disparities may further exacerbate human rights issues and widen the increasingly divergent approaches to HIV prevention, care and treatment.

HIV transmission only occurs from people with HIV, and viral load is the single greatest risk factor for all modes of transmission. HAART can lower viral load to nearly undetectable levels. Prevention of mother to child transmission offers proof of the concept of HAART interrupting transmission, and observational studies and previous modelling work support using HAART for prevention. Although knowing one's HIV status is key for prevention efforts, it is not known with certainty when to start HAART.

Building on previous modelling work, we used an HIV/AIDS epidemic of South African intensity to explore the impact of testing all adults annually and starting persons on HAART immediately after they are diagnosed as HIV positive. This theoretical strategy would reduce annual HIV incidence and mortality to less than one case per 1000 people within 10 years and it would reduce the prevalence of HIV to less than 1% within 50 years. To explore HAART as a prevention strategy, we recommend further discussions to explore human rights and ethical considerations, clarify research priorities and review feasibility and acceptability issues.

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New heterosexually transmitted HIV infections in married or cohabiting couples in urban Zambia and Rwanda: an analysis of survey and clinical data.

Kristin L. Dunkle, Rob Stephenson, Etienne Karita … (2008)

Sub-Saharan Africa has a high rate of HIV infection, most of which is attributable to heterosexual transmission. Few attempts have been made to assess the extent of HIV transmission within marriages, and HIV-prevention efforts remain focused on abstinence and non-marital sex. We aimed to estimate the proportion of heterosexual transmission of HIV which occurs within married or cohabiting couples in urban Zambia and Rwanda each year. We used population-based data from Demographic and Health Surveys (DHS) on heterosexual behaviour in Zambia in 2001-02 and in Rwanda in 2005. We also used data on the HIV serostatus of married or cohabiting couples and non-cohabiting couples that was collected through a voluntary counselling and testing service for urban couples in Lusaka, in Zambia, and Kigali, in Rwanda. We estimated the probability that an individual would acquire an incident HIV infection from a cohabiting or non-cohabiting sexual partner, and then the proportion of total heterosexual HIV transmission which occurs within married or cohabiting couples in these settings each year. We analysed DHS data from 1739 Zambian women, 540 Zambian men, 1176 Rwandan women, and 606 Rwandan men. Under our base model, we estimated that 55.1% to 92.7% of new heterosexually acquired HIV infections among adults in urban Zambia and Rwanda occurred within serodiscordant marital or cohabiting relationships, depending on the sex of the index partner and on location. Under our extended model, which incorporated the higher rates of reported condom use that we found with non-cohabiting partners, we estimated that 60.3% to 94.2% of new heterosexually acquired infections occurred within marriage or cohabitation. We estimated that an intervention for couples which reduced transmission in serodiscordant urban cohabiting couples from 20% to 7% every year could avert 35.7% to 60.3% of heterosexually transmitted HIV infections that would otherwise occur. Since most heterosexual HIV transmission for both men and women in urban Zambia and Rwanda takes place within marriage or cohabitation, voluntary counselling and testing for couples should be promoted, as should other evidence-based interventions that target heterosexual couples.

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Early Antiretroviral Therapy Reduces AIDS Progression/Death in Individuals with Acute Opportunistic Infections: A Multicenter Randomized Strategy Trial

Andrew Zolopa, Janet Andersen, Lauren Komarow … (2009)

Background Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined. Methods and Findings A5164 was a randomized strategy trial of “early ART” - given within 14 days of starting acute OI treatment versus “deferred ART” - given after acute OI treatment is completed. Randomization was stratified by presenting OI and entry CD4 count. The primary week 48 endpoint was 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression with incomplete viral suppression (ie HIV viral load (VL) ≥50 copies/ml); 3. No progression with optimal viral suppression (ie HIV VL <50 copies/ml). Secondary endpoints included: AIDS progression/death; plasma HIV RNA and CD4 responses and safety parameters including IRIS. 282 subjects were evaluable; 141 per arm. Entry OIs included Pneumocytis jirovecii pneumonia 63%, cryptococcal meningitis 12%, and bacterial infections 12%. The early and deferred arms started ART a median of 12 and 45 days after start of OI treatment, respectively. The difference in the primary endpoint did not reach statistical significance: AIDS progression/death was seen in 20 (14%) vs. 34 (24%); whereas no progression but with incomplete viral suppression was seen in 54 (38%) vs. 44 (31%); and no progression with optimal viral suppression in 67 (48%) vs 63 (45%) in the early vs. deferred arm, respectively (p = 0.22). However, the early ART arm had fewer AIDS progression/deaths (OR = 0.51; 95% CI = 0.27–0.94) and a longer time to AIDS progression/death (stratified HR = 0.53; 95% CI = 0.30–0.92). The early ART had shorter time to achieving a CD4 count above 50 cells/mL (p<0.001) and no increase in adverse events. Conclusions Early ART resulted in less AIDS progression/death with no increase in adverse events or loss of virologic response compared to deferred ART. These results support the early initiation of ART in patients presenting with acute AIDS-related OIs, absent major contraindications. Trial Registration ClinicalTrials.gov NCT00055120

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Short-term and long-term risk of tuberculosis associated with CD4 cell recovery during antiretroviral therapy in South Africa.

Landon Myer, Robin Wood, David Edwards … (2009)

To determine the short-term and long-term risks of tuberculosis (TB) associated with CD4 cell recovery during antiretroviral therapy (ART). Observational community-based ART cohort in South Africa. TB incidence was determined among patients (n = 1480) receiving ART for up to 4.5 years in a South African community-based service. Updated CD4 cell counts were measured 4-monthly. Person-time accrued within a range of CD4 cell count strata (CD4 cell strata) was calculated and used to derive CD4 cell-stratified TB rates. Factors associated with incident TB were identified using Poisson regression models. Two hundred and three cases of TB were diagnosed during 2785 person-years of observation (overall incidence, 7.3 cases/100 person-years). During person-time accrued within CD4 cell strata 0-100, 101-200, 201-300, 301-400, 401-500 and more than 500 cells/microl unadjusted TB incidence rates were 16.8, 9.3, 5.5, 4.6, 4.2 and 1.5 cases/100 person-years, respectively (P < 0.001). During early ART (first 4 months), adjusted TB rates among those with CD4 cell counts 0-200 cells/microl were 1.7-fold higher than during long-term ART (P = 0.026). Updated CD4 cell counts were the only patient characteristic independently associated with long-term TB risk. Updated CD4 cell counts were the dominant predictor of TB risk during ART in this low-resource setting. Among those with baseline CD4 cell counts less than 200 cells/microl, the excess adjusted risk of TB during early ART was consistent with 'unmasking' of disease missed at baseline screening. TB incidence rates at CD4 cell counts of 200-500 cells/microl remained high and adjunctive interventions are required. TB prevention would be improved by ART policies that minimized the time patients spend with CD4 cell counts below a threshold of 500 cells/microl.

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Journal ID (nlm-ta): J Int AIDS Soc

Title: Journal of the International AIDS Society

Publisher: BioMed Central

ISSN (Electronic): 1758-2652

Publication date Collection: 2010

Publication date (Electronic): 12 January 2010

Volume: 13

Page: 1

Affiliations

[1 ]Department of HIV/AIDS, World Health Organization, Geneva, Switzerland

[2 ]HTM, World Health Organization, Geneva, Switzerland

[3 ]UNAIDS India, Delhi, India

[4 ]Centers for Disease Control Kenya, Kenya

[5 ]South African Centre for Epidemiological Modelling and Analysis, Stellenbosch, South Africa

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Publisher ID: 1758-2652-13-1

DOI: 10.1186/1758-2652-13-1

PMC ID: 2822750

PubMed ID: 20205768

SO-VID: afd36c24-846a-4928-b1b3-36e342cb9dd9

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This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Highly active antiretroviral treatment for the prevention of HIV transmission

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Most cited references 24

New heterosexually transmitted HIV infections in married or cohabiting couples in urban Zambia and Rwanda: an analysis of survey and clinical data.

Early Antiretroviral Therapy Reduces AIDS Progression/Death in Individuals with Acute Opportunistic Infections: A Multicenter Randomized Strategy Trial

Short-term and long-term risk of tuberculosis associated with CD4 cell recovery during antiretroviral therapy in South Africa.

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