Chloroquine and Hydroxychloroquine for the Prevention or Treatment of Novel Coronavirus Disease (COVID-19) in Africa: Caution for Inappropriate Off-Label Use in Healthcare Settings

The novel severe acute respiratory syndrome-coronavirus-2 pandemic has spread to Africa, where nearly all countries have reported laboratory-confirmed cases of novel coronavirus disease (COVID-19). Although there are ongoing clinical trials of repurposed and investigational antiviral and immune-based therapies, there are as yet no scientifically proven, clinically effective pharmacological treatments for COVID-19. Among the repurposed drugs, the commonly used antimalarials chloroquine (CQ) and hydroxychloroquine (HCQ) have become the focus of global scientific, media, and political attention despite a lack of randomized clinical trials supporting their efficacy. Chloroquine has been used worldwide for about 75 years and is listed by the WHO as an essential medicine to treat malaria. Hydroxychloroquine is mainly used as a therapy for autoimmune diseases. However, the efficacy and safety of CQ/HCQ for the treatment of COVID-19 remains to be defined. Indiscriminate promotion and widespread use of CQ/HCQ have led to extensive shortages, self-treatment, and fatal overdoses. Shortages and increased market prices leave all countries vulnerable to substandard and falsified medical products, and safety issues are especially concerning for Africa because of its healthcare system limitations. Much needed in Africa is a cross-continental collaborative network for coordinated production, distribution, and post-marketing surveillance aligned to low-cost distribution of any approved COVID-19 drug; this would ideally be piggybacked on existing global aid efforts. Meanwhile, African countries should strongly consider implementing prescription monitoring schemes to ensure that any off-label CQ/HCQ use is appropriate and beneficial during this pandemic

Mortality from HIV-associated meningitis in sub-Saharan Africa: a systematic review and meta-analysis.

INTRODUCTION: HIV-associated cryptococcal, TB and pneumococcal meningitis are the leading causes of adult meningitis in sub-Saharan Africa (SSA). We performed a systematic review and meta-analysis with the primary aim of estimating mortality from major causes of adult meningitis in routine care settings, and to contrast this with outcomes from clinical trial settings. METHODS: We searched PubMed, EMBASE and the Cochrane Library for published clinical trials (defined as randomized-controlled trials (RCTs) or investigator-managed prospective cohorts) and observational studies that evaluated outcomes of adult meningitis in SSA from 1 January 1990 through 15 September 2019. We performed random effects modelling to estimate pooled mortality, both in clinical trial and routine care settings. Outcomes were stratified as short-term (in-hospital or two weeks), medium-term (up to 10 weeks) and long-term (up to six months). RESULTS AND DISCUSSION: Seventy-nine studies met inclusion criteria. In routine care settings, pooled short-term mortality from cryptococcal meningitis was 44% (95% confidence interval (95% CI):39% to 49%, 40 studies), which did not differ between amphotericin (either alone or with fluconazole) and fluconazole-based induction regimens, and was twofold higher than pooled mortality in clinical trials using amphotericin based treatment (21% (95% CI:17% to 25%), 17 studies). Pooled short-term mortality of TB meningitis was 46% (95% CI: 33% to 59%, 11 studies, all routine care). For pneumococcal meningitis, pooled short-term mortality was 54% in routine care settings (95% CI:44% to 64%, nine studies), with similar mortality reported in two included randomized-controlled trials. Few studies evaluated long-term outcomes. CONCLUSIONS: Mortality rates from HIV-associated meningitis in SSA are very high under routine care conditions. Better strategies are needed to reduce mortality from HIV-associated meningitis in the region

PLoS Med

BACKGROUND: The effect of antiretroviral treatment (ART) eligibility expansions on patient outcomes, including rates of timely ART initiation among those enrolling in care, has not been assessed on a large scale. In addition, it is not known whether ART eligibility expansions may lead to "crowding out" of sicker patients. METHODS AND FINDINGS: We examined changes in timely ART initiation (within 6 months) at the original site of HIV care enrollment after ART eligibility expansions among 284,740 adult ART-naive patients at 171 International Epidemiology Databases to Evaluate AIDS (IeDEA) network sites in 22 countries where national policies expanding ART eligibility were introduced between 2007 and 2015. Half of the sites included in this analysis were from Southern Africa, one-third were from East Africa, and the remainder were from the Asia-Pacific, Central Africa, North America, and South and Central America regions. The median age of patients enrolling in care at contributing sites was 33.5 years, and the median percentage of female patients at these clinics was 62.5%. We assessed the 6-month cumulative incidence of timely ART initiation (CI-ART) before and after major expansions of ART eligibility (i.e., expansion to treat persons with CD4 </= 350 cells/muL [145 sites in 22 countries] and CD4 </= 500 cells/muL [152 sites in 15 countries]). Random effects metaregression models were used to estimate absolute changes in CI-ART at each site before and after guideline expansion. The crude pooled estimate of change in CI-ART was 4.3 percentage points (95% confidence interval [CI] 2.6 to 6.1) after ART eligibility expansion to CD4 </= 350, from a baseline median CI-ART of 53%; and 15.9 percentage points (pp) (95% CI 14.3 to 17.4) after ART eligibility expansion to CD4 </= 500, from a baseline median CI-ART of 57%. The largest increases in CI-ART were observed among those newly eligible for treatment (18.2 pp after expansion to CD4 </= 350 and 47.4 pp after expansion to CD4 </= 500), with no change or small increases among those eligible under prior guidelines (CD4 </= 350: -0.6 pp, 95% CI -2.0 to 0.7 pp; CD4 </= 500: 4.9 pp, 95% CI 3.3 to 6.5 pp). For ART eligibility expansion to CD4 </= 500, changes in CI-ART were largest among younger patients (16-24 years: 21.5 pp, 95% CI 18.9 to 24.2 pp). Key limitations include the lack of a counterfactual and difficulty accounting for secular outcome trends, due to universal exposure to guideline changes in each country. CONCLUSIONS: These findings underscore the potential of ART eligibility expansion to improve the timeliness of ART initiation globally, particularly for young adults

Impact de Ia chimioprophylaxie au cotrimoxazole sur Ia morbidite infectieuse non palustre chez des adultes Ouest Africains vivant avec le VIH

L' objectif de notre etude a ete de decrire la morbidite infectieuse non palustre au sein de la cohorte MALHIV des patients vivant avec le VlH (PVVlH) ; exposes ou non a la chimioprophylaxie au cotrimoxazole. 11 s'est agi d'une etude descriptive nichee au sein de la cohorte MALlliV, prospective, longitudinale, multicentrique, comparative menee dans quatre services d'infectiologie (Abidjan, Bamako, Dakar, BoboDioulasso), chez des patients infectes par le VIH suivis depuis au moins 12 mois. Le critere de jugement principal a ete !'incidence cumulee de la morbidite infectieuse non palustre au cours du suivi apres !'inclusion des patients dans I' etude. Notre etude a porte sur 527 patients ayant un age moyen de 37 ans, unsex ratio de 0,44, repartis en 2 groupes: un groupe expose au cotrimoxazole, groupe CTX $ (64,5 %) et un groupe non expose, groupe CTX 8 (35,5 %). A I' inclusion le taux de CD4 moyen etait de 287,9 ce1l/mm3 et la charge virale moyenne etait de 5,8 log10. Les 2/3 des patients ont ete rnis sous traitement antiretroviral.L'incidence cumulee des evenements infectieux non palustres a ete de 54,6% avec un taux d'incidence de 36,4/100 pers-annees. Le taux d'incidence de la morbidite infectieuse severe a ere de 12,6/100 pers-annees, dominee par la tuberculose. Les etiologies bacteriennes ont ere majoritairement retrouvees dans les 2 bras. Le taux d'incidence dans le bras CTX 8 a ete 26, 6/100 pers-annees vs 11,6/100  persannees dans le bras CTXEB, avec une difference statistiquement significative (p &lt; 0.05). Les evenements non classant SIDA ont ete retrouves majoritairement dans le bras non expose avec une incidence de 21.6% vs 7.6% dans le bras expose, un taux de reduction de 60% (P &lt; 0.05). Notre etude confirme le role protecteur de la chimioprophylaxie au cotrimoxazole sur la morbidite infectieuse non palustre et souligne l'interet des nouvelles recommandations OMS suggerant de prescrire le cotrimoxazole aux PVVIH quelque soit le taux de CD4 tout  particulierement dans les pays ou predorninent les infections bacteriennes et le paludisme.Mots-cles : Morbidire, Cotrimoxazole, VIH, Afrique

HIV Treatment Produces Economic Returns Through Increased Work And Education, And Warrants Continued US Support

Federal expenditures are under scrutiny in the United States, and the merits of continuing and expanding the President’s Emergency Plan for AIDS Relief (PEPFAR) to support access to antiretroviral therapy have become a topic of debate. A growing body of research on the economic benefits of treatment with antiretroviral therapy has important implications for these discussions. For example, research conducted since the inception of PEPFAR shows that HIV-infected adults who receive antiretroviral therapy often begin or resume productive work, and that children living in households with infected adults who are on treatment are more likely to attend school than those in households with untreated adults. These benefits should be considered when weighing the overall benefits of providing antiretroviral therapy against its costs, particularly in the context of discussions about the future of PEPFAR. A modest case can also be made in favor of having private companies in HIV-affected countries provide antiretroviral therapy to their employees and dependents, thus sharing some of the burden of funding HIV treatment

Aging with HIV: what effect on mortality and loss to follow-up in the course of antiretroviral therapy? The IeDEA West Africa Cohort Collaboration

Charlotte Bernard,1,2 Eric Balestre,1,2 Patrick A Coffie,3&ndash;5 Serge Paul Eholie,3,4 Eug&egrave;ne Messou,3&ndash;6 Viviane Kwaghe,7 Benson Okwara,8 Adrien Sawadogo,9 Yao Abo,10 Fran&ccedil;ois Dabis,1,2 Nathalie de Rekeneire1,2 On behalf of the International Epidemiological Database to evaluate Aids (IeDEA) West Africa Collaboration 1INSERM, Centre INSERM U1219-Epid&eacute;miologie-Biostatistique, Bordeaux, France; 2University of Bordeaux, School of Public Health (ISPED), Bordeaux, France; 3D&eacute;partement de Dermatologie et d&rsquo;Infectiologie, UFR des Sciences M&eacute;dicales, Universit&eacute; F&eacute;lix Houphou&euml;t Boigny, Abidjan, C&ocirc;te d&rsquo;Ivoire; 4Unit of Infectious and Tropical Diseases, Treichville University Teaching Hospital, Abidjan, C&ocirc;te d&rsquo;Ivoire; 5Programme PAC-CI, Treichville University Teaching Hospital, Abidjan, Ivory Coast; 6Center of Care, Research and Training (CePReF), Yopougon-Atti&eacute; Hospital, Abidjan, Ivory Coast; 7University of Abuja Teaching Hospital, Abuja, Nigeria; 8University of Benin City Teaching Hospital, Benin City, Nigeria; 9Institut Sup&eacute;rieur des Sciences de la Sant&eacute; (INSSA), Bobo-Dioulasso Polytechnic University, Bobo-Dioulasso, Burkina Faso; 10National Blood Transfusion Center (CNTS), Abidjan, Ivory Coast Background: Reporting mortality and lost to follow-up (LTFU) by age is essential as older HIV-positive patients might be at risk of long-term effects of living with HIV and/or taking antiretroviral therapy (ART). As age effects might not be linear and might impact HIV outcomes in the oldest more severely, people living with HIV (PLHIV) aged 50&ndash;59 years and PLHIV aged &gt;60 years were considered separately.Setting: Seventeen adult HIV/AIDS clinics spread over nine countries in West Africa.Methods: Data were collected within the International Epidemiological Databases to Evaluate AIDS West Africa Collaboration. ART-na&iuml;ve PLHIV-1 adults aged &gt;16 years initiating ART and attending &ge;2 clinic visits were included (N=73,525). Age was divided into five groups: 16&ndash;29/30&ndash;39/40&ndash;49/50&ndash;59/&ge;60 years. The age effect on mortality and LTFU was evaluated with Kaplan&ndash;Meier curves and multivariable Cox proportional hazard regressions.Results: At month 36, 5.9% of the patients had died and 47.3% were LTFU. Patients aged &ge;60 (N=1,736) and between 50&ndash;59 years old (N=6,792) had an increased risk of death in the first 36 months on ART (adjusted hazard ratio=1.66; 95% CI: 1.36&ndash;2.03 and adjusted hazard ratio=1.31; 95% CI: 1.15&ndash;1.49, respectively; reference: &lt;30 years old). Patients &ge;60 years old tend to be more often LTFU.Conclusion: The oldest PLHIV presented the poorest outcomes, suggesting that the PLHIV aged &gt;50 years old should not be considered as a unique group irrespective of their age. Tailored programs focusing on improving the care services for older PLHIV in Sub-Saharan Africa are clearly needed to improve basic program outcomes. Keywords: HIV, aging, ART, mortality, lost to follow-up, Sub-Saharan Afric

Efficacy and safety of two dosages of cotrimoxazole as preventive treatment for HIV-infected Malawian adults with new smear-positive tuberculosis.

OBJECTIVE: To assess the efficacy and safety of two different dosages of cotrimoxazole (CTX) in prophylaxis in HIV-positive new smear-positive pulmonary tuberculosis (TB) patients in Blantyre, Malawi. METHOD: Randomized, double-blind trial using 480 and 960 mg of CTX given to new TB patients, who were followed up until the end of the tuberculosis treatment. The primary outcome was survival. The outcome in the two groups was also compared with an unselected cohort of similar patients registered in Zomba, Malawi in 1995 and new smear-positive patients registered in the National Tuberculosis Programme in 1999. The secondary outcome was the occurrence of (opportunistic) events, especially bacterial pneumonia. RESULTS: There were no statistically significant differences in mortality and bacterial pneumonia between the groups receiving the two different dosages. The case fatality rate at the end of the tuberculosis treatment was 15.4% in the 480 mg group and 14.0% in the 960 mg group. This was lower than the case fatality rate in the Zomba cohort (19.2%, P = 0.10) and lower than the case fatality rate in the national programme (21.0%, P < 0.001). CTX was well tolerated. Compliance was fair. CONCLUSIONS: CTX prophylaxis may have a beneficial effect on mortality and morbidity in HIV-infected smear-positive tuberculosis patients in Malawi. The efficacy of both dosages is not significantly different. The intervention is cheap and easy to implement. These results would support implementation of CTX in this patient group until better strategies are available or evidence is convincingly presented to suggest that its benefit is marginal