Gender differences in clinical and immunological outcomes in South African HIV-infected patients on HAART

ABSTRACT Introduction South Africa is estimated to have the largest number of HIV infected adults in Southern Africa with a higher HIV prevalence in females compared to males. While significant reductions in morbidity and mortality due to HIV and AIDS have been realized for over a decade internationally, HIV treatment involving highly active antiretroviral therapy (HAART) is still a relatively new phenomenon in this country and gender differences in HIV outcomes between males and females in South Africa have not been previously well described. This study aimed to determine and describe gender differences in clinical and immunological outcomes in a population of HIV infected South African adults initiated on HAART. Materials and Methods This retrospective data analysis reviewed 6,617 HIV-infected adultsABSTRACT Introduction South Africa is estimated to have the largest number of HIV infected adults in Southern Africa with a higher HIV prevalence in females compared to males. While significant reductions in morbidity and mortality due to HIV and AIDS have been realized for over a decade internationally, HIV treatment involving highly active antiretroviral therapy (HAART) is still a relatively new phenomenon in this country and gender differences in HIV outcomes between males and females in South Africa have not been previously well described. This study aimed to determine and describe gender differences in clinical and immunological outcomes in a population of HIV infected South African adults initiated on HAART. Materials and Methods This retrospective data analysis reviewed 6,617 HIV-infected adults initiated on HAART at the Themba Lethu Clinic, an urban public-sector antiretroviral rollout facility in Johannesburg, South Africa between 1st April 2004 and 31st March 2007. Clinical data from these antiretroviral naïve patients was analysed for gender differences in mortality, rates of loss to follow up, CD4 cell count response, virologic suppression and weight gain. Cox regression models and logistic regression models were used to estimate hazard ratios (HR) and odds ratios (OR), respectively, for associations between gender and outcomes. Models were adjusted for age and baseline CD4 count. Results At baseline, 4,388 (66.3%) women were significantly younger (p<0.0001) and less likely to be employed than the 2,229 (33.7%) men (p<0.001). Furthermore, women had significantly higher baseline CD4 counts (p<0.0001) and higher body mass index (BMI) (p<0.0001). Males experienced significantly reduced survival compared to females (p=0.0053) by Kaplan-Meier analysis. In adjusted multivariate analysis, men were 22% more likely to die or become lost to follow up than women [HR = 1.22 (95% CI 1.06 - 1.39]. The period with the highest risk of mortality or loss to follow up was within six months of starting HAART. Female gender was associated with better CD4 count response. In multivariate analysis adjusted for age and baseline CD4 count, women were 35% more likely to achieve a 100 cell increase in CD4 count at four months after initiation of HAART [OR =1.35 (95% CI = 1.19 -1.54)] and 45% more likely to increase their CD4 counts by 100 cells/mm3 after ten months on HAART [OR =1.42 (95% CI = 1.20 -1.68)] when compared to men. Women were also more likely to achieve virologic suppression at ten months post HAART initiation [OR =1.54 (95% CI =1.21-1.97)] and were more likely to have gained weight after four months on treatment than males [OR = 1.26 (95% CI = 1.07–1.49)] after adjusting for age, baseline CD4 count and baseline BMI. Conclusions Women had significant advantages over men in terms of short-term clinical and immunological outcomes. Earlier access treatment for men should be facilitated and adherence should be promoted once on treatment. Further research is required to determine if these gender differences persist during long-term HAART

Mobility and Clinic Switching Among Postpartum Women Considered Lost to HIV Care in South Africa.

This version is the Accepted Manuscript, and was published in final edited form as: J Acquir Immune Defic Syndr. 2017 April 01; 74(4): 383–389. doi:10.1097/QAI.0000000000001284OBJECTIVE: Retention in HIV care, particularly among postpartum women, is a challenge to national antiretroviral therapy programs. Retention estimates may be underestimated because of unreported transfers. We explored mobility and clinic switching among patients considered lost to follow-up (LTFU). DESIGN: Observational cohort study. METHODS: Of 788 women initiating antiretroviral therapy during pregnancy at 6 public clinics in Johannesburg, South Africa, 300 (38.1%) were LTFU (no visit ≥3 months). We manually searched for these women in the South African National Health Laboratory Services database to assess continuity of HIV care. We used geographic information system tools to map mobility to new facilities. RESULTS: Over one-third (37.6%) of women showed evidence of continued HIV care after LTFU. Of these, 67.0% continued care in the same province as the origin clinic. Compared with those who traveled outside of the province for care, these same-province "clinic shoppers" stayed out-of-care longer {median 373 days [interquartile range (IQR): 175-790] vs. 175.5 days (IQR: 74-371)} and had a lower CD4 cell count on re-entry [median 327 cells/μL (IQR: 196-576) vs. 493 cells/μL (IQR: 213-557). When considering all women with additional evidence of care as engaged in care, cohort LTFU dropped from 38.1% to 25.0%. CONCLUSION: We found evidence of continued care after LTFU and identified local and national clinic mobility among postpartum women. Laboratory records do not show all clinic visits and manual matching may have been under- or overestimated. A national health database linked to a unique identifier is necessary to improve reporting and patient care among highly mobile populations

Effectiveness and safety of 30 mg versus 40 mg stavudine regimens: a cohort study among HIV-infected adults initiating HAART in South Africa

<p>Abstract</p> <p>Background</p> <p>As stavudine remains an important and widely prescribed drug in resource-limited settings, the effect of a reduced dose of stavudine (from 40 mg to 30 mg) on outcomes of highly active antiretroviral therapy (HAART) remains an important public health question.</p> <p>Methods</p> <p>We analyzed prospectively collected data from the Themba Lethu Clinic in Johannesburg, South Africa. We assessed the relationship between stavudine dose and six- and/or 12-month outcomes of stavudine substitution, failure to suppress viral load to below 400 copies/ml, development of peripheral neuropathy, lipoatrophy and hyperlactatemia/lactic acidosis. Since individuals with a baseline weight of less than 60 kg were expected to have received the same dose of stavudine throughout the study period, analysis was restricted to individuals who weighed 60 kg or more at baseline. Data were analyzed using logistic regression.</p> <p>Results</p> <p>Between 1 April 2004 and 30 September 2009, 3910 patients were initiated on antiretroviral therapy (ART) with a recorded stavudine dose and were included in the analysis. Of these, 2445 (62.5%) received a 40 mg stavudine dose while 1565 (37.5%) received 30 mg. In multivariate analysis, patients receiving a 40 mg dose were more likely to discontinue stavudine use (adjusted odds ratio, OR 1.71; 95% confidence limits, CI 1.13-2.57) than those receiving 30 mg by 12 months on ART. Additionally, patients receiving 40 mg doses of stavudine were more likely to report peripheral neuropathy (OR 3.12; 95% CI 1.86-5.25), lipoatrophy (OR 11.8; 95% CI 3.2-43.8) and hyperlactatemia/lactic acidosis (OR 8.37; 95% CI 3.83-18.29) in the same time period. Failure to suppress HIV viral load within 12 months of HAART initiation was somewhat more common among those given 40 mg doses (OR 1.62; 95% CI 0.88, 2.97) although this result lacked precision. Sensitivity analyses accounting for death and loss to follow up generally supported these estimates.</p> <p>Conclusions</p> <p>Lower stavudine dosage is associated with fewer reports of several stavudine-associated adverse events and also a lower risk of stavudine discontinuation within the first year on ART.</p

CD4+ gain percentile curves for monitoring response to antiretroviral therapy in HIV-infected adults

We constructed CD4 count gain percentile distributions standardized by baseline CD4 count and assessed the association between poor CD4 count gain and subsequent death and virological failure on antiretroviral treatment (ART)

Pregnancy and Virologic Response to Antiretroviral Therapy in South Africa

Although women of reproductive age are the largest group of HIV-infected individuals in sub-Saharan Africa, little is known about the impact of pregnancy on response to highly active antiretroviral therapy (HAART) in that setting. We examined the effect of incident pregnancy after HAART initiation on virologic response to HAART.We evaluated a prospective clinical cohort of adult women who initiated HAART in Johannesburg, South Africa between 1 April 2004 and 30 September 2009, and followed up until an event, death, transfer, drop-out, or administrative end of follow-up on 31 March 2010. Women over age 45 and women who were pregnant at HAART initiation were excluded from the study; final sample size for analysis was 5,494 women. Main exposure was incident pregnancy, experienced by 541 women; main outcome was virologic failure, defined as a failure to suppress virus to ≤ 400 copies/ml by six months or virologic rebound >400 copies/ml thereafter. We calculated adjusted hazard ratios using marginal structural Cox proportional hazards models and weighted lifetable analysis to calculate adjusted five-year risk differences. The weighted hazard ratio for the effect of pregnancy on time to virologic failure was 1.34 (95% confidence limit [CL] 1.02, 1.78). Sensitivity analyses generally confirmed these main results.Incident pregnancy after HAART initiation was associated with modest increases in both relative and absolute risks of virologic failure, although uncontrolled confounding cannot be ruled out. Nonetheless, these results reinforce that family planning is an essential part of care for HIV-positive women in sub-Saharan Africa. More work is needed to confirm these findings and to explore specific etiologic pathways by which such effects may operate

Prevalence and predictors of kaposi sarcoma herpes virus seropositivity: a cross-sectional analysis of HIV-infected adults initiating ART in Johannesburg, South Africa

<p>Abstract</p> <p>Background</p> <p>Kaposi sarcoma (KS) is the most common AIDS-defining tumour in HIV-infected individuals in Africa. Kaposi sarcoma herpes virus (KSHV) infection precedes development of KS. KSHV co-infection may be associated with worse outcomes in HIV disease and elevated KSHV viral load may be an early marker for advanced HIV disease among untreated patients. We examined the prevalence of KSHV among adults initiating antiretroviral therapy (ART) and compared immunological, demographic and clinical factors between patients seropositive and seronegative for KSHV.</p> <p>Results</p> <p>We analyzed cross-sectional data collected from 404 HIV-infected treatment-naïve adults initiating ART at the Themba Lethu Clinic, Johannesburg, South Africa between November 2008 and March 2009. Subjects were screened at ART initiation for antibodies to KSHV lytic K8.1 and latent Orf73 antigens. Seropositivity to KSHV was defined as positive to either lytic KSHV K8.1 or latent KSHV Orf73 antibodies. KSHV viremia was determined by quantitative PCR and CD3, 4 and 8 lymphocyte counts were determined with flow cytometry. Of the 404 participants, 193 (48%) tested positive for KSHV at ART initiation; with 76 (39%) reactive to lytic K8.1, 35 (18%) to latent Orf73 and 82 (42%) to both. One individual presented with clinical KS at ART initiation. The KSHV infected group was similar to those without KSHV in terms of age, race, gender, ethnicity, smoking and alcohol use. KSHV infected individuals presented with slightly higher median CD3 (817 vs. 726 cells/mm³) and CD4 (90 vs. 80 cells/mm³) counts than KSHV negative subjects. We found no associations between KSHV seropositivity and body mass index, tuberculosis status, WHO stage, HIV RNA levels, full blood count or liver function tests at initiation. Those with detectable KSHV viremia (n = 19), however, appeared to present with signs of more advanced HIV disease including anemia and WHO stage 3 or 4 defining conditions compared to those in whom the virus was undetectable.</p> <p>Conclusions</p> <p>We demonstrate a high prevalence of KSHV among HIV-infected adults initiating ART in a large urban public-sector HIV clinic. KSHV viremia but not KSHV seropositivity may be associated with markers of advanced HIV disease.</p

Prevalent tuberculosis and mortality among HAART initiators

The effect of tuberculosis on mortality in people initiating highly active antiretroviral treatment (HAART) remains unclear; here, we strengthened a previous cohort analysis. Multivariate Cox proportional hazards models were used to assess the association of baseline tuberculosis and time to all-cause mortality among HAART initiators. In reanalysis, treatment for tuberculosis at time of HAART initiation remained unassociated with increased risks of all-cause mortality, with adjusted hazard ratios ranging from 1.00 to 1.09

Incidence of Pregnancy after Initiation of Antiretroviral Therapy in South Africa: A Retrospective Clinical Cohort Analysis

Background. Little is known about rates of incident pregnancy among HIV-positive women initiating highly active antiretroviral therapy (HAART). Methods. We conducted a retrospective clinical cohort study among therapy-naïve women ages 18–45 initiating HAART between 1 April 2004 and 30 September 2009 at an adult HAART clinic in Johannesburg, South Africa. We used Poisson regression to characterize rates and rate ratios of pregnancy. Results. We evaluated 5,996 women who experienced 727 pregnancies during 14,095 person-years at risk. The overall rate of pregnancy was 5.2 per 100 person-years (95% confidence limits [CL] 4.8, 5.5). By six years, cumulative incidence of first pregnancy was 22.9% (95% CL 20.6%, 25.4%); among women ages 18–25 at HAART initiation, cumulative incidence was 52.2% (95% CL 35.0%, 71.8%). The strongest predictor of incidence of pregnancy was age, with women 18–25 having 13.2 times the rate of pregnancy of women ages 40–45 in adjusted analysis. CD4 counts below 100 and worse adherence to HAART were associated with lower rates of incident pregnancy. Conclusions. Women experience high rates of incident pregnancy after HAART initiation. Understanding which women are most likely to experience pregnancy will help planning and future efforts to understand the implications of pregnancy for response to HAART

Kaposi's Sarcoma Associated-Herpes Virus (KSHV) Seroprevalence in Pregnant Women in South Africa

<p>Abstract</p> <p>Background</p> <p>Factors previously associated with Kaposi's sarcoma-associated herpesvirus (KSHV) transmission in Africa include sexual, familial, and proximity to river water. We measured the seroprevalence of KSHV in relation to HIV, syphilis, and demographic factors among pregnant women attending public antenatal clinics in the Gauteng province of South Africa.</p> <p>Methods</p> <p>We tested for antibodies to KSHV lytic K8.1 and latent Orf73 antigens in 1740 pregnant women attending antenatal clinics who contributed blood to the "National HIV and Syphilis Sero-Prevalence Survey - South Africa, 2001". Information on HIV and syphilis serology, age, education, residential area, gravidity, and parity was anonymously linked to evaluate risk factors for KSHV seropositivity. Clinics were grouped by municipality regions and their proximity to the two main river catchments defined.</p> <p>Results</p> <p>KSHV seropositivity (reactive to either lytic K8.1 and latent Orf73) was nearly twice that of HIV (44.6% vs. 23.1%). HIV and syphilis seropositivity was 12.7% and 14.9% in women without KSHV, and 36.1% and 19.9% respectively in those with KSHV. Women who are KSHV seropositive were 4 times more likely to be HIV positive than those who were KSHV seronegative (AOR 4.1 95%CI: 3.4 - 5.7). Although, women with HIV infection were more likely to be syphilis seropositive (AOR 1.8 95%CI: 1.3 - 2.4), no association between KSHV and syphilis seropositivity was observed. Those with higher levels of education had lower levels of KSHV seropositivity compared to those with lower education levels. KSHV seropositivity showed a heterogeneous pattern of prevalence in some localities.</p> <p>Conclusions</p> <p>The association between KSHV and HIV seropositivity and a lack of common association with syphilis, suggests that KSHV transmission may involve geographical and cultural factors other than sexual transmission.</p

Cohort profile: the Right to Care Clinical HIV Cohort, South Africa

PURPOSE: The research objectives of the Right to Care Clinical HIV Cohort analyses are to: (1) monitor treatment outcomes (including death, loss to follow-up, viral suppression and CD4 count gain among others) for patients on antiretroviral therapy (ART); (2) evaluate the impact of changes in the national treatment guidelines around when to initiate ART on HIV treatment outcomes; (3) evaluate the impact of changes in the national treatment guidelines around what ART regimens to initiate on drug switches; (4) evaluate the cost and cost-effectiveness of HIV treatment delivery models; (5) evaluate the need for and outcomes on second-line and third-line ART; (6) evaluate the impact of comorbidity with non-communicable diseases on HIV treatment outcomes and (7) evaluate the impact of the switch to initiating all patients onto ART regardless of CD4 count. PARTICIPANTS: The Right to Care Clinical HIV Cohort is an open cohort of data from 10 clinics in two provinces within South Africa. All clinics include data from 2004 onwards. The cohort currently has data on over 115 000 patients initiated on HIV treatment and patients are followed up every 3–6 months for clinical and laboratory monitoring. FINDINGS TO DATE: Cohort data includes information on demographics, clinical visit, laboratory data, medication history and clinical diagnoses. The data have been used to identify rates and predictors of first-line failure, to identify predictors of mortality for patients on second-line (eg, low CD4 counts) and to show that adolescents and young adults are at increased risk of unsuppressed viral loads compared with adults. FUTURE PLANS: Future analyses will inform national models of HIV care and treatment to improve HIV care policy in South Africa