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This study investigated the relationship between highly active antiretroviral therapy (HAART) and instrumental activities of daily living (IADLs) among two clinical cohorts in South Africa. Between 2003 and 2008 structured questionnaires were administered to HIV-positive patients attending outpatient clinics at an urban hospital (Soweto, n = 3,081) and a rural hospital (Acornhoek, n = 1,247). Among those receiving help, an average of 4.8 and 5.1 h of assistance with IADLs daily was reported (rural and urban participants, respectively), with the patient's mother and children assisting the most. Participants on HAART were 17 and 41% less likely to receive assistance with IADLs in the rural and urban cohorts, respectively, after adjusting for demographic characteristics, healthcare utilization, and CD4 counts. HAART significantly decreased the IADL assistance among patients in South Africa. Alongside clinical benefits, HAART has the potential to reduce the burden of HIV-related care, potentially extending wider social and economic gains to other family members. [ABSTRACT FROM AUTHOR]

Background: Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drugrefill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa. Methods: In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12-99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL.50 copies/ml) and immunologic failure (as defined by WHO). Results: After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of ,95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p,0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2-6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2- 3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02). Conclusion: One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure. [ABSTRACT FROM AUTHOR]

The HIV epidemic in sub-Saharan Africa disproportionately affects women of reproductive age. The increasing provision of Highly Active Anti-Retroviral Therapy (HAART) with improved prognosis and maternal-fetal outcomes calls for an understanding of fertility planning for HIV-positive women. We describe the effect of HIV and HAART on pregnancy desires and contraceptive use among HIV-positive women in Soweto, South Africa. Focus group discussions and in-depth interviews were conducted with 42 HIV-positive women of reproductive age. Analysis was performed using ATLAS-ti (ATLAS-ti Center, Berlin). Emergent themes were impact of HIV diagnosis on pregnancy intentions; factors affecting contraceptive uptake including real and normative side effects, body image, and perceived vaginal wetness; and the mitigating influence of partnership on both pregnancy intentions and contraceptive use. Routine counseling about pregnancy desires and contraception should be offered to HIV-positive women. [ABSTRACT FROM AUTHOR]

The article focuses on the study on the cost of providing care for HIV infected adults in an urban HIV clinic in Soweto, South Africa. The study assesses the costs of initiating and maintaining patients on antiretroviral therapy, highlighting the program planning, budgeting and cost-effectiveness analyses. Methods and results of the study are included, concluding the high cost of treating HIV-infected patients in the month of initiation and lower cost for stable patients.

This research explores the short-term socioeconomic effect of antiretroviral treatment (ART) in HIV positive patients attending the Perinatal HIV Research Unit clinics in Soweto, South Africa. An overall increase in mean personal and household income following commencement of ART was noted. Mean personal income rose 53% over baseline income. A decrease in the number of meals missed in households was noted in 10% of the sample. The leading themes regarding income were change in employment status and social grants. Antiretroviral treatment increased the capacity to seek employment and unemployed individuals were actively searching for work. Patients noted an improvement in well-being, with fewer to no episodes of illness, and improved quality of life from three months after starting ART. The empirical evidence suggests that individuals gain substantial benefits from being on ART despite the socioeconomic challenges in South Africa. [ABSTRACT FROM AUTHOR]

Abstract: Background: Contraceptive preferences of HIV-infected women must be considered in efforts to integrate HIV and reproductive health services. In South Africa, contraception is often discontinued due to bleeding pattern changes. It is unknown whether HIV-infected women are more sensitive to menstrual changes and how this affects contraceptive choice. This study describes perceptions toward menses and contraceptive-induced amenorrhea among HIV-infected women. Study Design: A convenience sample of 42 HIV-infected women aged 15 to 45 years was purposively recruited for three focus groups and 15 in-depth qualitative interviews which were conducted at the Perinatal HIV Research Unit, South Africa. Transcripts were coded and emergent themes grouped. Results: One third of women reported HIV-related menstrual changes, unchanged by antiretroviral use. Menstruation was believed to purge the body of “dirty blood.” Women perceived that menstruation had a negative effect on male partner sexual desire, with concern about higher HIV transmission during menstruation. Ninety-six percent of injectable contraceptive users experienced amenorrhea, regarded as troublesome and a reason for discontinuation. Conclusion: In Soweto, HIV diagnosis may accentuate linking menstruation with health, leading to avoidance or discontinuation of methods causing amenorrhea. Providers should intensify education on the safety of contraceptive-induced oligo/amenorrhea. [Copyright &y& Elsevier]

Background: Tuberculosis (TB) is a common infection in people living with HIV. However, the risk factors for HIV/TB co-infection in second-line HIV therapy are poorly understood. We aimed to determine the incidence and risk factors for TB co-infection in SECOND-LINE, an international randomized clinical trial of second-line HIV therapy., Methods: We did a cohort analysis of TB cases in SECOND-LINE. TB cases included any clinical or laboratory-confirmed diagnoses and/or commencement of treatment for TB after randomization. Baseline factors associated with TB were analyzed using Cox regression stratified by site., Results: TB cases occurred at sites in Argentina, India, Malaysia, Nigeria, South Africa, and Thailand, in a cohort of 355 of the 541 SECOND-LINE participants. Overall, 20 cases of TB occurred, an incidence rate of 3.4 per 100 person-years (95% CI: 2.1 to 5.1). Increased TB risk was associated with a low CD4+-cell count (≤200 cells/μL), high viral load (>200 copies/mL), low platelet count (<150 ×109/L), and low total serum cholesterol (≤4.5 mmol/L) at baseline. An increased risk of death was associated with TB, adjusted for CD4, platelets, and cholesterol. A low CD4+-cell count was significantly associated with incident TB, mortality, other AIDS diagnoses, and virologic failure., Discussion: The risk of TB remains elevated in PLHIV in the setting of second-line HIV therapy in TB endemic regions. TB was associated with a greater risk of death. Finding that low CD4+ T-cell count was significantly associated with poor outcomes in this population supports the value of CD4+ monitoring in HIV clinical management., Competing Interests: R.T.H. is supported by an Australian Government Research Training Program (RTP) Scholarship; M.N.P. is supported by fellowships from the Cancer Institute NSW and National Health and Medical Research Council; M. Law is supported by an investigator grant from the National Health and Medical Research Council. The other authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

South African (SA) researchers have made both national and global contributions to HIV prevention and treatment. Research conducted in SA has contributed markedly to improved survival in HIV-infected infants, children and adults. The translation of clinical research into practice has enabled the curtailment of paediatric HIV in SA. Along with international collaborators, SA has made pivotal contributions to biomedical prevention modalities including medical male circumcision and oral and topical microbicides, and is undertaking pivotal HIV vaccine research. Research into the structural and psychosocial drivers of HIV infection will be critical for sustaining biomedical interventions, and necessary to end AIDS.

Objective: To report the viral load and CD4 count in HIV-infected, antiretroviral naïve, first -time HIV-testers, not immediately eligible for treatment initiation by current South Africa treatment guidelines., Design: This was a cross-sectional study in a high-volume, free-of-charge HIV testing centre in Soweto, South Africa., Methods: We enrolled first time HIV testers and collected demographic and risk-behaviour data and measured CD4 count and viral load., Results: Between March and October 2011, a total of 4793 adults attended VCT and 1062 (22%) tested positive. Of the 1062, 799 (75%) were ART naïve and 348/799 (44%) were first-time HIV testers. Of this group of 348, 225 (65%) were female. Overall their median age, CD4 count and viral load was 34 years (IQR: 28-41), 364 (IQR: 238-542) cells/mm3 and 13,000 (IQR: 2050-98171) copies/ml, respectively. Female first time HIV testers had higher CD4 counts (419 IQR: 262-582 vs. 303 IQR: 199-418 cells/mm3) and lower viral loads (9,100 vs. 34,000 copies/ml) compared to males. Of 183 participants with CD4 count >350 cells/mm3, 62 (34%) had viral loads > 10,000 copies/ml., Conclusions: A large proportion of HIV infected adults not qualifying for immediate ART at the CD4 count threshold of 350 cells/mm3 have high viral loads. HIV-infected men at their first HIV diagnosis are more likely to have lower CD4 counts and higher viral loads than women.

Objective: We hypothesize that time to initiate care and maturity of a treatment program impact on outcome of severely immuno-compromised patients with higher risk of mortality., Design: We conducted a retrospective cohort analysis at the Perinatal HIV Research Unit Adult ART clinic, Soweto, South Africa., Methods: ELIGIBILITY CRITERIA FOR THIS ANALYSIS WERE: attendance for minimum one visit between August 2004 and August 2010, age >18 years, CD4 count < 50 cells/mm(3) and ART-naïve at screening. We followed participants up to one year after ART initiation. We defined years 2004-2007 and 2008-2010 as the early and late eras respectively. Chi-square test and survival analysis methods were used for mortality comparisons between eras., Results: Of 2357 patients eligible for antiretroviral treatment, 395 (17%) had CD4 counts < 50 cells/mm(3) and ART-naïve at screening. Overall 261 (66%) were women. Patients had similar median age (35 vs. 33.5 years, p=0.08), time to HAART initiation (7 days, p=0.18) and baseline CD4 count (20 vs. 23 cells/mm(3), p=0.5) between eras. Overall 63 (16%) patients died in their first year of treatment (2 per 100 person-months) and the main cause of death was tuberculosis (n=23, 37%). The proportion of deaths (52/262 vs. 11/133, p=0.003) and time to death from enrolment (logrank p=0.04) were significantly different between eras., Conclusion: Mortality decreased as the ART program matured in Soweto while time to initiation of treatment remained similar in both eras. Because ART guidelines were consistent during both eras, it is possible that with time, management of patients improved as expertise was gained.

Few studies have compared hospitalizations before and after antiretroviral therapy (ART) initiation in the same patients. We analyzed the cost of hospitalizations among 3906 adult patients in 2 South African hospitals, 30% of whom initiated ART. Hospitalizations were 50% and 40% more frequent and 1.5 and 2.6 times more costly at a CD4 cell count, 100 cells/mm(3) when compared with 200–350 cells/mm(3) in the pre-ART and ART period, respectively. Mean inpatient cost per patient year was USD 117 (95%confidence interval, 85 to 158) for patients on ART and USD 72(95% confidence interval, 56 to 89) for pre-ART patients. Raising ART eligibility thresholds could avoid the high cost of hospitalization before and immediately after ART initiation.

Objective: To determine the impact of HAART on incidence, regression, and progression of cytopathological abnormalities in HIV-infected women., Design: Prospective cohort., Methods: HIV-infected women (N=1123) from Soweto, South Africa underwent serial cervical smears that were analyzed and reported using the Bethesda System. The results of HAART and non-HAART users were compared using two statistical approaches: a survival analysis assessing risk of incident smear abnormality among women with baseline normal smear results; and analysis with marginal models assessing for an association between HAART use and likelihood of regression/progression in consecutive smears., Results: After multivariate survival analysis, women using HAART with a normal baseline smear were 38% less likely to have an incident smear abnormality during follow-up than nonusers [confidence interval (CI) 0.42-0.91; P=0.01]. Multivariate marginal models analysis identified a significantly increased likelihood (odds ratio 2.61; CI 1.75-3.89; P<0.0001) of regression of cervical lesions among women on HAART., Conclusion: Our large prospective cohort study adds significant weight to the side of the balance of clinical research supporting the positive impact of HAART on the natural history of human papillomavirus-related cervical disease in HIV-infected women., (© 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins)

Objective: To ascertain progression and regression of cervical dysplasia in HIV-infected women in Soweto., Design: Prospective cohort., Methods: Women attending an HIV wellness clinic were offered cervical smears as part of care; smears were assessed using the Bethesda system. Those with high-grade lesions or worse were referred for colposcopy. Progression analyses included women with at least two smears at least 5.5 months apart. Hazard ratios were used to ascertain predictors of progression., Results: Two thousand, three hundred and twenty-five women had a baseline smear; their median age and CD4 cell count was 32 years and 312 cells/μl, respectively; 17% were taking highly active antiretroviral therapy (HAART); 62, 20 and 14% had normal, low-grade squamous intraepithelial lesions (LSIL) or high-grade squamous intraepithelial lesions (HSIL), respectively. Of those with baseline normal or LSIL smears, 1074 had another smear; progression from normal to LSIL was 9.6/100 person-years (95% CI 8.3-11.1) and progression from normal or LSIL to HSIL was 4.6/100 person-years (95% CI 3.9-5.5). Of 225 women with LSIL at baseline and at least one subsequent smear at least 11.5 months later, 44.0% regressed to normal (21.2/100 person-years (95% CI 17.5-25.7)). Multivariate models suggested increasing risk for progression in women with CD4 cell count below 500 cells/μl and HAART may reduce the risk of progression [adjusted hazard ratio (aHR) 0.72 (0.52-0.99)]., Conclusion: HIV-infected women have high rates of prevalent and incident HSIL and LSIL with relatively low risk of regression to normal from LSIL. HAART appears to protect against progression. Our findings suggest cervical screening intervals should be less than 10 years - irrespective of age in women with CD4 cell counts below 500 cells/μl.

Objective: In light of increasing access to HAART in sub-Saharan Africa, we conducted a longitudinal study to assess the impact of HAART on sexual risk behaviors among HIV-infected South Africans in urban and rural primary care clinics., Design: Prospective observational cohort., Methods: We conducted a cohort study at rural and urban primary care HIV clinics in South Africa consisting of 1544 men and 4719 women enrolled from 2003 to 2010, representing 19703 clinic visits. The primary outcomes were being sexually active, unprotected sex, and more than one sex partner and were evaluated at 6 monthly intervals. Generalized estimated equations assessed the impact of HAART on sexual risk behaviors., Results: Among 6263 HIV-infected men and women, over a third (37.2%) initiated HAART during study follow-up. In comparison to pre-HAART follow-up, visits while receiving HAART were associated with a decrease in those reporting being sexually active [adjusted odds ratio: 0.86 (95% confidence interval: 0.78-0.95)]. Unprotected sex and having more than one sex partner were reduced at visits following HAART initiation compared to pre-HAART visits [adjusted odds ratio: 0.40 (95% confidence interval: 0.34-0.46) and adjusted odds ratio: 0.20 (95% confidence interval: 0.14-0.29), respectively]., Conclusion: Sexual risk behavior significantly decreased following HAART initiation among HIV-infected South African men and women in primary care programs. The further expansion of antiretroviral treatment programs could enhance HIV prevention efforts in Africa.

Objective: Little is known about the temporal impact of the rapid scale-up of large antiretroviral therapy (ART) services on programme outcomes. We describe patient outcomes [mortality, loss-to-follow-up (LTFU) and retention] over time in a network of South African ART cohorts., Design: Cohort analysis utilizing routinely collected patient data., Methods: Analysis included adults initiating ART in eight public sector programmes across South Africa, 2002-2007. Follow-up was censored at the end of 2008. Kaplan-Meier methods were used to estimate time to outcomes, and proportional hazards models to examine independent predictors of outcomes., Results: Enrolment (n = 44 177, mean age 35 years; 68% women) increased 12-fold over 5 years, with 63% of patients enrolled in the past 2 years. Twelve-month mortality decreased from 9% to 6% over 5 years. Twelve-month LTFU increased annually from 1% (2002/2003) to 13% (2006). Cumulative LTFU increased with follow-up from 14% at 12 months to 29% at 36 months. With each additional year on ART, failure to retain participants was increasingly attributable to LTFU compared with recorded mortality. At 12 and 36 months, respectively, 80 and 64% of patients were retained., Conclusion: Numbers on ART have increased rapidly in South Africa, but the programme has experienced deteriorating patient retention over time, particularly due to apparent LTFU. This may represent true loss to care, but may also reflect administrative error and lack of capacity to monitor movements in and out of care. New strategies are needed for South Africa and other low-income and middle-income countries to improve monitoring of outcomes and maximize retention in care with increasing programme size.

Background: We assessed risk factors for viremia and drug resistance among long-term recipients of antiretroviral therapy (ART) in South Africa., Methods: In 2008, we conducted a cross-sectional study among patients receiving ART for 12 months or more. Genotypic resistance testing was performed on individuals with a viral load higher than 400 RNA copies/ml. Multiple logistic regression analysis was used to assess associations., Results: Of 998 participants, 75% were women with a median age of 41 years. Most (64%) had been on treatment for more than 3 years. The prevalence of viremia was 14% (n = 139): 12% (102/883) on first-line [i.e. nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen] and 33% (37/115) on second-line (i.e. protease inhibitor (PI)-based regimen) ART. Of viremic patients, 78% had drug resistance mutations. For NRTIs, NNRTIs and PIs, the prevalence of mutations was 64, 81 and 2%, respectively, among first-line failures and 29, 54 and 6%, respectively, among second-line failures. M184V/I, K103N and V106A/M were the most common mutations. Significant risk factors associated with viremia on first-line regimen included concurrent tuberculosis treatment [odds ratio (OR) 6.4, 95% confidence interval (CI) 2.2-18.8, P < 0.01] and a recent history of poor adherence (OR 2.7, 1.3-5.6, P = 0.01). Among second-line failures, attending a public clinic (OR 4.6, 95% CI 1.8-11.3, P < 0.01) and not having a refrigerator at home (OR 6.7, 95% CI 1.2-37.5, P = 0.03) were risk factors for virological failure., Conclusion: Risk factors for viral failure were line regimen dependent. Second-line ART recipients had a higher rate of viremia, albeit with infrequent PI drug resistance mutations. Measures to maintain effective virologic suppression should include increased adherence counseling, attention to concomitant tuberculosis treatment and heat-stable formulations of second-line ART regimens.

Background: High BMI has been shown to be protective against tuberculosis (TB) among HIV-uninfected individuals, as well as against disease progression and mortality among those with HIV. We examined the effect of BMI on all-cause mortality and TB incidence among a cohort of HIV-infected adults in Soweto, South Africa., Methods: A clinical cohort of 3456 HIV-infected adults from South Africa was prospectively followed from 2003 to 2008 with regular monitoring. The primary exposure was BMI and the outcomes of interest were all-cause mortality and a newly diagnosed episode of TB. Cox proportional hazard models assessed associations with risk of mortality or incident TB., Results: Incidence rates of mortality were 10.4/100 person-years for baseline BMI of 18.5 or less, 3.6/100 person-years for baseline BMI 18.6-25, 1.7/100 person-years for baseline BMI 25.1-30, and 1.6/100 person-years for baseline BMI more than 30. Compared to those with normal BMI, overweight and obese participants had a significantly reduced risk of mortality [adjusted hazard ratio 0.59 (95% confidence interval, CI 0.40-0.87) and 0.48 (95% CI 0.29-0.80), respectively]. Incidence rates of TB by baseline BMI were 7.3/100 person-years for underweight, 6.0/100 person-years for normal, 3.2/100 person-years for overweight, and 1.9/100 person-years for obese. Compared to those with normal BMI, those with overweight and obese BMI were at a significantly reduced risk of developing TB [adjusted hazard ratio 0.56 (95% CI 0.38-0.83) and 0.33 (95% CI 0.19-0.55), respectively]., Conclusion: HIV-infected individuals with obese and overweight BMI have a significantly reduced risk of both mortality and TB, after adjusting for HAART use and CD4 cell count.

Objectives: To introduce the combined South African cohorts of the International epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterise patients accessing these services; and to describe changes in services and patients from 2003 to 2007., Design and Setting: Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal., Subjects: Adults and children (<16 years old) who initiated ART with > or =3 antiretroviral drugs before 2008., Results: Most sites were offering free treatment to adults and children in the public sector, ranging from 264 to 17,835 patients per site. Among 45,383 adults and 6,198 children combined, median age (interquartile range) was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5), respectively. Of adults, 68% were female. The median CD4 cell count was 102 cells/microl (44-164) and was lower among males than females (86, 34-150 v. 110, 50-169, p<0.001). Median CD4% among children was 12% (7-17.7). Between 2003 and 2007, enrolment increased 11-fold in adults and 3-fold in children. Median CD4 count at enrolment increased for all adults (67-111 cells/microl, p<0.001) and for those in stage IV (39-89 cells/microl, p<0.001). Among children <5 years, baseline CD4% increased over time (11.5-16.0%, p<0.001)., Conclusions: IeDEA-SA provides a unique opportunity to report on the national ART programme. The study describes dramatically increased enrolment over time. Late diagnosis and ART initiation, especially of men and children, need attention. Investment in sentinel sites will ensure good individual-level data while freeing most sites to continue with simplified reporting.

Background: The World Health Organization recommends isoniazid preventive therapy (IPT) for preventing tuberculosis in HIV-infected adults, although few countries have instituted this policy. Both IPT and highly active antiretroviral therapy (HAART) used separately result in reductions in tuberculosis risk. There is less information on the combined effect of IPT and HAART. We assessed the effect of IPT, HAART or both IPT and HAART on tuberculosis incidence in HIV-infected adults in South Africa., Methods: Two clinical cohorts of HIV-infected patients were studied. Primary exposures were receipt of IPT and/or HAART and the primary outcome was incident tuberculosis. Crude incident rates and incident rate ratios were calculated and Cox proportional hazards models investigated associations with tuberculosis risk., Results: Among 2778 HIV-infected patients followed for 4287 person-years, 267 incident tuberculosis cases were diagnosed [incidence rate ratio (IRR)=6.2/100 person-years; 95% CI 5.5-7.0]. For person-time without IPT or HAART, the IRR was 7.1/100 person-years (95% CI 6.2-8.2); for person-time receiving HAART but without IPT, the IRR was 4.6/100 person-years (95% CI 3.4-6.2); for person-time after IPT but prior to HAART, the IRR was 5.2/100 person-years (95% CI 3.4-7.8); during follow-up in patients treated with HAART after receiving IPT the IRR was 1.1/100 person-years (95% CI 0.02-7.6). Compared to treatment-naive patients, HAART-only patients had a 64% decreased hazard for tuberculosis [adjusted hazard ratio (aHR)=0.36; 95% CI 0.25-0.51], and patients receiving HAART after IPT had a 89% reduced hazard (aHR=0.11; 95% CI 0.02-0.78)., Conclusion: Tuberculosis risk is significantly reduced by IPT in HAART-treated adults in a high-incidence operational setting in South Africa. IPT is an inexpensive and cost-effective strategy and our data strengthen calls for the implementation of IPT in conjunction with the roll-out of HAART.